In the aftermath of a disastrous experiment gone wrong, a city finds itself overrun with the undead due to a virus released by the mega-corporation Umbrella Corporation. As the infection rapidly spreads, the city is sealed off in a containment effort to prevent the global spread of the virus, trapping both the infected and uninfected citizens inside. Among those trapped is Alice, who has escaped from an Umbrella research facility and is experiencing side effects from exposure to the virus, giving her enhanced physical abilities.

Efforts to survive in the quarantined city bring human survivors together, including a suspended police officer, a journalist, and other disparate individuals, all fighting for survival. As they navigate the chaos, they are constantly thwarted by hoards of zombies and the menacing Nemesis, a bio-engineered Umbrella Corporation operative assigned to eliminate all potential witnesses to the outbreak. Amidst battles for survival and the search for a way out, the group learns of a potential escape plan that involves a time-sensitive rendezvous point, putting them under even more pressure to find a way out of the nightmarish urban landscape overrun by the infectious undead.