Years after the outbreak of the T-virus, the Earth has become a desolate wasteland overrun by the undead. Former Umbrella Corporation employee, Alice, has been bio-engineered with superhuman abilities and is constantly on the run from the corporation that wants to recapture and control her. As she travels through the Nevada desert, she seeks to evade Umbrella's surveillance systems and satellites, while battling the zombie hordes and other mutated creatures that pepper the landscape.

Alice discovers a journal detailing the supposed last safe human haven free from infection, located in Alaska. Concurrently, a convoy of survivors, led by Claire Redfield and Carlos Olivera, traverses the wasteland in search of supplies and safety. As they grapple with the harsh realities of a world overrun by the infected, their paths cross with Alice's. The group decides to band together, with the hope of making it to Alaska, but not before Umbrella's latest experiments in the form of enhanced zombies and other monstrosities come hunting for them, bringing the fight to a new level of danger and desperation.