Resident Evil Zero is a third-person survival horror video game and a prequel to the first Resident Evil. The gameplay remains largely the same as previous entries in the series but also introduces what it calls a partner zapping system, which allows you to switch between the two characters Rebecca and Billy at any time. This feature must be used at times, as the game requires both characters to work together to solve some puzzles. New to the game are a bunch of terrifying enemies, like the mutant centipede, new areas to explore, and the ability to drop items on the ground instead of having to find an item box.

On July 23, 1998, special police STARS Bravo team is sent in to investigate a series of grisly murders in the Arklay Mountains region outside of Raccoon City. On the way to the scene, Bravo's helicopter malfunctions and is forced to crash-land in the forest. The team soon discover an overturned military police transport truck, along with the mutilated corpses of two officers. The team split up and Bravo team's field medic, Rebecca Chambers, finds a train stopped in the middle of the forest. Rebecca soon discovers that the train, the Ecliptic Express, is infested with zombies.