Unlike Resident Evil 5 and Resident Evil 6, the gameplay emphasizes horror and exploration over action. The inventory uses a grid-based system with an initial capacity of 12 slots, but may be expanded several times over the course of the game. An item can occupy up to two spaces, and four items may be assigned to the D-pad. Item boxes found in save rooms may also be used to manage and store items, and can be retrieved from different item boxes for later use. Items in the inventory can be used, examined, or combined with other items to increase their usefulness. Many of the game's puzzles require that items be examined under certain conditions in order to reveal secrets. Tape recorders can be used to manually save the game's progress, which, depending on the given difficulty level, may require the use of a cassette tape. Videotapes are scattered for Ethan to find, which place the player in the perspective of a different character, oftentimes revealing plot information or clues needed to solve a puzzle.
The PlayStation 4 version of the game is playable in virtual reality using the PlayStation VR headset, with the core gameplay mechanics remaining identical. The game will be playable on VR devices compatible with Microsoft Windows and Xbox One in 2018.