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A Gotham City, il comico Arthur Fleck con problemi di malattia mentale viene disprezzato dalla società. Inizia una spirale verso il basso di rivolte e crimini sanguinanti. Questo lo mette faccia a faccia con il suo alter ego: "il Joker".

Z, a vicious genetic scientist, discovers a way to alter harmless humanoid androids called 'Cyborgs' into becoming killing machines, which he plans to use for his own gain.

FBI Agent Elizabeth Farrell is in charge of tracking down death row escapee William Tate but is informed by the Director of the FBI that for reasons unknown, Bo Adams is traveling with him. He makes it clear that Bo is far more important than Tate and Farrell is subsequently briefed by geneticist Roman Skouris about her abilities. Bo and Tate meanwhile are on their way to the safe house in Philadelphia but have to stop in Atlantic City on the way. They have no money - something they rectify by having Bo help Tate at the craps table. Bo decides to help a waitress whose 5 year-old son is quite ill but Farrell and her team are quickly homing on them.

Gordon works in a monster-ridden Gotham as a bounty hunter and seeks to find answers about the Indian Hill escapees and why their powers appear to be killing them. Bruce's doppelganger roams the streets and Barbara and Tabitha open a nightclub called The Sirens.

Fish Mooney takes matters into her own hands to locate Hugo Strange, forcing Gordon to reluctantly team up with journalist Valerie Vale to find her. Penguin rises in popularity after criticizing the work of the GCPD, and Bruce's investigation of the Court of Owls is compromised. Meanwhile, Ivy Pepper is reintroduced into Gotham.