The game takes place over a six day span in New York City in 1997. The incident starts on December 24 and ends on December 29.
The game begins with Aya Brea, an NYPD rookie, attending an opera with an unnamed date. During the opera, everyone in the building spontaneously combusts, except for Aya, her date, and an actress on stage named Melissa Pearce. Aya confronts Melissa backstage, and Melissa says that Aya’s mitochondria need more time to develop. Melissa then mutates into a beast and flees into the sewers, declaring that her name is now Eve.
The game opens to reveal Aya Brea who is now an FBI operative in their Mitochondrial Investigation and Suppression Team (MIST) being dispatched on an urgent mission in central Los Angeles, where there have been reports of NMC sightings. The first chapter in the game puts Aya in the position of investigating the Akropolis tower where she finds a slaughtered SWAT team and an NMC infestation. She soon discovers that the NMC's can take on human form, and eventually encounters a different type of creature; a humanoid Artificial Neo-Mitochondrial Creature (ANMC) called Golem No.9. Returning to the shelter, and reunited with Kyle, Aya rescues a girl that has been manipulated into controlling the hostile NMC's.She also finds out that the girl, Eve Brea was created from her own DNA, making her, in a sense, Aya's daughter. Eve Brea is later kidnapped by No.9.