The game will be played from a first-person perspective. Players will be able to use weapons to fight back against enemies, although the developers say they should not expect a "gun fest". Other popular elements of Resident Evil games, such as puzzle-solving, resource management and healing herbs have also been confirmed to feature in the game. Quick time events, on the other hand, will be entirely absent. The PlayStation 4 version of the game can also be played from start to finish in VR using the PlayStation VR helmet, but gameplay remains identical between the two modes.
The game is set after Resident Evil 6, "in modern day", and features a new main character that does not have the combat skills the main characters of recent Resident Evil games display. Although connections to previous games in the series exist, there will not be any returning characters. The game's setting is described as a derelict plantation mansion in rural America. The title of the game, which for the first time contains in it both the "Resident Evil" and "Biohazard" brand names of the series, is said to be a clue to what's behind the game's plot.