Resident Evil 0 Biohazard 0 HD Remaster is a prequel to the original Resident Evil, following S.T.A.R.S. medic Rebecca Chambers and escaped convict Billy Coen as they uncover the first signs of the outbreak aboard a stranded train and beyond.

Players switch between the two partners at will, combining their skills to solve puzzles and survive. Without item boxes, supplies must be dropped and carried carefully, adding a distinct layer of classic survival horror resource management.