R?MJ: The Mystery Hospital is an interactive movie horror adventure game with full voice-acting. The story takes place in a General Hospital, where a large explosion occurred due to a deadly virus release. The hospital is on lockdown, and you are trapped with no way out. You assume the role of Hajime, who was visiting his friend when he found himself stuck inside with two friends, Ryou and Tomowo, and a rookie nurse, Aya.
The gameplay involves exploring locations in the hospital by moving forward, turning left or right, or turning back. The movement uses pre-rendered animation for every step. You can zoom in on certain locations to gather more details or pick up items. Your companions will often comment while you explore, with comments that are randomly selected from five possible sentences. The game also features the use of your senses (sight, hearing, touch, smell, and taste) at key points to progress.