-Patricia and Marie are orphans and slaves (most likely to the medici family), the former having been too defiant to give in to her master's demands, she is brutally beaten, dismembered and blinded by the heads there, made as an example for any other possible future rebels. Traumatized by the brutal maiming of her best friend, Marie flees the house and arrives to the Grand cathedral for sanctuary, where Double lures her to the Skullheart, convincing her to wish on it. Marie wishes for the total eradication of the Medici mafia, and her violent wish is deemed impure. She is made into the next Skullgirl.
-After catching frequencies and traces of a new Skullgirl emerging, the ASG Labs quickly deploy The Last Hope to attack her while it's early and possibly kill her. Double is ready, however, and she and Marie kill all of the Last Hope but one, deciding to spare Valentine if she agreed to serve the Skullgirl. Valentine begrudgingly accepts.
-Filia and Carol are best friends in a school at Maplecrest. However, an unknown event occurs, implied to involve ASG Lab 0, the lab that Brain Drain operates in. The 2 girls are separated and Filia awakens sometime later with no memories and a parasite on her head in place of her hair: The vulgar but powerful Samson.
-A group of dagonian thieves from Little Innsmouth named "The Fishbone Gang" run rampant throughout New Meridian. One member, Nadia Fortune, successfully infiltrates Medici Tower(as the Medicis have now grown into a city-wise underground force) and steals the Life Gem from Lorenzo, crippling his figure and causing him to retreat from the public spotlight. When Lorenzo orders his men to kill the thieves and retrieve the Gem, they catch and brutally dice the Fishbone gang, killing every one of them but Ms Fortune, who had actually consumed the Life Gem beforehand and was granted immortality by it.
-Around this time, Princess Parasoul, now the commander of her army as well as the Black Egrets, is informed that the newest Skullgirl has emerged. Marie has begun to reveal herself, and Parasoul and the Black Egrets dispatch posthaste. Princess Umbrella, the then-infant sister of Parasoul, begins exhibiting strange behavior and wanders out of the palace on her own.
-Behind Marie's back, Valentine collaborates with Brain Drain to create an Anti-Skullgirl weapon unlike any other. They plan to use not one, but 2 synthetic parasities to guarantee victory. Additonally, Valentine inserts some of the Skullgirl's blood into the subject's body to equip her with a natural ability to sense the Skullheart as well as provide her with a boost of power. Brain Drain, on his part, uses his psychic powers to program her brain so that she will always serve her creators loyally. The Project is given the power to create sharp constructs from her blood and a large bladed wheel that emerges from her back; The subject is in fact Carol, Filia's best friend, who is renamed "Painwheel" by Lab 0.
-On the other end, Lab 8, the only other lab to have survived the years(?) and home to Big Band and Illeum among others, also decides to create a perfect Skullgirl hunting machine, theirs going in a completely different direction. Once again opting to add not one, but two synthetic parasites. The caring, yet firm good doctor Avian oversees the Project; she is granted a large radius sight and Skullgirl-disrupting Z-rays, as well as access to the entirety of Lab 8's gauntlet; the subject is in fact Patricia, Marie's best friend, who is renamed "Peacock" by Lab 8.
-Marie, still wishing to kill the Medicis, is lead by Double to Maplecrest, home of some medici-related families. Double returns to the Grand Cathedral as Marie, who has begun revealing herself by going on a murder spree within Maplecrest, is quickly reported on hours after Parasoul hears about it.
-Meanwhile, Beowulf, a now retired middle-aged man living by himself is attacked by Grendel's arm, which he keeps as a trophy. He takes it to The Grand Cathedral, wrestling it along the way, asking Double who is under the guise of Sister Agatha to Exorcise it. Double removes the Skullgirls's influence over the dead from it, and warns Beowulf to relinquish the limb. However, he decides to do the opposite and plans to make a comeback to the wrestling scene and regain the spotlight. Double sees this as an opportunity and takes the form of Beowulf's old agent Zane, offering him the opportunity to re-become the hero he once was by taking down the variety of parasite-wielders, cyborgs, mutants and the likes roaming New Meridian's streets, although in reality she means the main cast and all who serve as her obstacles.
-Cerebella, a young acrobat for the Cirque Des Cartes, a Medici-sponsored circus/hitman group, is offered the chance to fight in an exhibition match against her hero, the wrestler Beowulf to aid in his comeback. She excitedly fights him in the ring and probably gets her living weapon Vice-Versa signed afterwards.
-Painwheel, in a fit of rage at the people who turned her into a monster, escapes Lab 0. Valentine hears of her escape and secretly takes off after her, searching in the streets of New Meridian.
-Parasoul, en route while hunting the Skullgirl in Little Innsmouth, finds Ms Fortune, who is still wanted for thievery. They fight briefly and Nadia escapes.
-Peacock, detecting high Theonite radiation, begins to hunt the Skullgirl. She searches through New Meridian and encounters Filia, who is also searching for the Skullgirl to wish her memories back. Filia and Samson engage Peacock, believing her to be able to lead them to the Skullheart; they are vanquished by Peacock who’s superior arsenal knocks them out of the way.
-Valentine encounters Painwheel in Maplecrest, as she is after revenge on her and Brain Drain. They fight briefly before Valentine executes a command, which triggers Painwheel to rebel further. Angered at her creators for messing with her mind, she flees the scene, and Valentine runs off after her. Painwheel takes refuge in Little Innsmouth for the night.
-Double, who is now aware of Painwheel through her own means, takes on the guise of Zane and tricks Beowulf into searching Little Innsmouth for the cyborg teenager. He finds her and, believing it to be a wrestling match, fights Painwheel, injuring both him and her. Painwheel eventually escapes him, and, believing him to be from Lab 0, runs deeper into Little Innsmouth as Beowulf returns to New Meridian.
-Valentine, who is still searching through New Meridian for Painwheel, meets Beowulf. Learning that he had met and fought Carol, she curiously tests him by fighting him herself. Despite her years of training and vast arsenal, Grendel’s arm overpowers her briefly and she opts to retreat, believing the fight to have been a waste of time. Beowulf goes home for the night, marking the fight as a victory.
-News spreads of Marie’s murderous Medici Massacre (Haha alliterations again), and Ms Fortune, still in Little Innsmouth, realizes her time is running out and sets off to challenge the Skullgirl and use it’s wish to revive The Fishbone Gang.
-As she searches for the Skullgirl, Fortune encounters Valentine, who is still out searching for Painwheel. She takes interest in Ms Fortune’s dismembering abilities and attempts to subdue and capture her for testing purposes. Fortune fights, but is overpowered by Valentine. Before she can capture her, however, Double emerges and reveals that her presence has been requested by Marie.
-Marie orders Valentine and Double to attack Lab 8, as they are creating soldiers and weapons that could kill her. Valentine begrudgingly accepts, and regretfully prepares and plans her attack.
-Meanwhile, as Peacock has yet to locate the Skullgirl, Big Band decides to head out and do some investigating himself. Wether he tells the others or not is up for debate, but he senses her presence in the River King Casino, and, knowing of her grudge against the Medicis, enters the building searching for Marie.
-Double begins to see resistance in the Skullgirl. She confers to the Trinity of this, and learns that they are unsatisfied with Marie. Double pleads with them and agrees to heading out and finding a possible new host. In the meantime, knowing of Big Band’s power, she once again disguises herself as Zane and tells Beowulf to head to the River King Casino for his “next big match”; she plans to use Beowulf to distract Ben from Lab 8 while she and Valentine attack it.
-Valentine keeps correspondence with Brain Drain since their time working together, while Brain Drain is skeptical, he reads through her notes of the Skullgirls’ whereabouts and the characters she meets.
-Beowulf enters the River King Casino and locates Big Band. He naively assumes it is another Wrestling match while Big Band assumes he’s a Medici hitman. The two men fight eachother and Beowulf holds Ben off. Minette, who is there “catering” the event, is captured by two of the Medici’s men (Lawrence and Riccardo?) while there.
-Meanwhile, Marie, Valentine and Double storm Lab 8. They destroy their equipment, burn their research and kill off their staff, especially seeking Dr Avian. While Avian hides within the lab, he attempts to contact his 2 other ASG units who are out on the field to help. While Peacock and Big Band receive his transmission, they are too late and Valentine finds him. Dr Avian is killed, Double and Marie leave and Valentine stays behind to terminate the little research that is left; Double secretly captures some of the Lab 8 females as possible Skullheart hosts.
-Brain Drain intercepts Dr Avian’s message to Ben and Patricia, discovering Valentine’s nature as a double agent. While he is able to keep his anger from overwhelming him in the moment, he reads through Valentine’s last letter to him, including a crude but enthusiastic hand drawing of Ms Fortune whom she had faced earlier. The excitement Valentine displays with Fortune is the last straw, and Brain Drain explodes with rage and pride, deciding to build his own version of Ms Fortune. He spends several hours but ultimately finishes his newest creation: Robo Fortune. He sends her out to capture the Skullheart and attack Valentine along the way, but secretly believes R Fortune to be underqualified and inept, and plans to create another when he finds the time and motivation to do so.
-Robo Fortune scans throughout New Meridian and eventually locates Valentine, who is just leaving Lab 8 through the secret exit after finishing up. She engages her and they fight fiercely before Valentine exclaims that they’re on the same side, both Anti-Skullgirl fighters. Robo Fortune reveals to her that Brain Drain has labeled Val a traitor and that she is a hindrance to the mission. Valentine, infuriated with Brain Drain’s ego, breaks off their partnership and escapes. Robo Fortune begins to have doubts over Brain Drain’s authority, and is coaxed into taking the New Meridian Rapid Transit by Double, who is disguised as Delilah.
-Meanwhile, Filia and Samson, who are still tearing through Medici goons and Dagonians alike searching for clues towards the Skull Heart, land themselves in Little Innsmouth in the dark of the night. Slightly unnerved, their fear only grows once they encounter the howling of Painwheel, calling Filia’s name. Filia fights out of self-defense and eventually subdues the monster, who tensely reveals herself as “Carol”. The name brings back memories for Filia but before she can press further with her old friend Painwheel believes Filia to have rejected her and flees to find Valentine once more. A now-conflicted Filia decides to board the New Meridian Rapid Transit to distract herself.
-Elsewhere in New Meridian, Peacock and Ben have left their respective fights (leaving behind a confused Beowulf, unsure of what happened and now slightly suspicious) and headed towards Lab 8. As Big Band investigates the scene, Peacock finds the mortally wounded Dr Avian and hears his last words, urging her to use her powers seriously and defeat The Skullgirl. She leaves the building and Big Band finds several incriminating clues, directing him towards a prime suspect.
-Outside, Peacock argues with the survivors of the Lab 8 attack, as they believe the best course of action is to hide out and attempt to recover anything that might’ve survived the battle, Peacock claims that she’s instead off to challenge the Skullgirl, now that she has a lead on her radiation. Ben arrives and objects, chastising her and ordering Patricia to slow down so that they can eventually locate and challenge the Skullheart as a team. Much to his chagrin and despite his efforts to subdue her, Peacock heads off alone to challenge the Skullgirl, confident in her abilities. Ben is told to go after her by the rest of Lab 8, including Illeum, who he is implied to have romantic feelings for(?).
-Filia and Robo Fortune encounter each other aboard the Transit, and R.Fortune, believing Filia to be a hindrance to the mission, attacks. Filia fights back and the two battle to a standstill before Samson launches Robo Fortune off the train.
-Not far away, Beowulf is sitting alone in the NMO Arena, his “home”, contemplating the situation. He is surprised by something crashing through the roof, and looks on to find Robo Fortune, who has crash-landed in the building. The two fight until Robo Fortune is contacted by Brain Drain and ordered to get back to the mission as fighting him is a waste of time. R.Fortune obliges, and Beowulf is left alone, until someone speaks up from behind him.
-Annie, who has been equally searching for the Skullgirl, spectated the last quarter of the fight, and mentions to Beowulf how he is now in something much bigger than himself or wrestling. Beowulf doesn’t recognize Annie from their time working together, however Annie still attempts to warn him not to pursue the Skullgirl or the characters that Zane pushes him to fight, seeing him as a sort of friend after their years on the set of Annie of The Stars. She hints to Beowulf’s famous match with Grendel being staged, but Beowulf, in confusion and denial, asks her to leave.
-Double has been gathering more and more possible hosts for the Skullheart behind Marie’s back. Marie exhibits more and more symptoms that show that she is resisting the Heart’s power, but upon suspecting that her “servant” is aiming to replace her, plans to do something big against the Medicis to prove herself as a powerful Skullgirl.
-Ms Fortune, who has now gotten into numerous fights, returns to Little Innsmouth for a brief rest, only to discover that Minette has been kidnapped. She meets Irven, a Private Investigator who is uncovering clues on the case of several dagonian kidnappings. Nadia volunteers to join him in the effort, believing that the Medicis are behind the kidnapping.
-Vitale, who has been ordered by Lorenzo to find Ms Fortune at all costs, has kidnapped Minette to lure her in. However, he grows impatient and instead enlists the help of the Cirque Des Cartes’ most powerful and capable member, not to mention his most loyal admirer Cerebella. He asks that she find Fortune and she accepts.
-Meanwhile, Lorenzo and the Medici family contact Eliza, who is still a famous celebrity and nightclub songstress. She has been skimming blood drives for the past years, keeping her bloodthirst and Sekhmet a secret to the general public. The Skullgirl is killing their men and causing them trouble, and, knowing of Eliza’s great power; blackmail her into hunting the Skullgirl. Eliza initially refuses, but ends up agreeing after being threatened by Black Dahlia. She is partnered with Cerebella who is tasked with overseeing Eliza’s progress while also keeping eye for Ms Fortune, who they suspect is nearby searching for Minette.
