On an isolated tropical island, a television crew takes part in a survival reality show when a series of disturbing events quickly turns the production into a nightmare. Infected creatures begin to appear, communications are cut off, and the participants realize they are trapped at the center of a new biological outbreak. Claire Redfield and BSAA agents are drawn into the incident in an effort to uncover the source of the infection and those responsible for the experiment. Between mutations, corporate secrets, and the struggle to survive, the island gradually reveals connections to the bioweapons that have continued to threaten the world since the events of Raccoon City.