The story begins at Brighton Beach in Brooklyn, New York City where XIII awakes, badly wounded and with no memory of his past. The game roughly follows the storyline of the first five volumes of the comic (the first fifteen issues), although there are several additions to the storyline, and changes were made to better adapt the story to game format. The game ends at the exact point where the comic's fifth volume ended, and as such, the complete story is unfinished, leaving room for a sequel.
Condemned: Criminal Origins, players take the role of Ethan Thomas, a SCU agent (Serial Crime Unit investigator that uses forensic tools) framed for a double cop murder who becomes trapped in the condemned sections of a fictional American city named "Metro City" while hunting a serial killer. Thomas' investigation is further complicated by a mysterious phenomenon that is transforming the transient population of these areas into insane, violent psychotics. As Thomas, the player investigates crime scenes using forensic tools and techniques, while fighting off the constant assaults by "the condemned" in the hopes of catching the serial killer and escaping alive, and prove that he is innocent to the police.