The House of the Dead is a rail shooter where you go through four chapters with branching paths, killing zombies while avoiding humans and rescuing a girl. You can also shoot special targets to get temporary health and weapon upgrades.
The game has two extra modes in its Saturn version: Saturn Mode and Boss Mode. In Saturn Mode, the gameplay is similar to the arcade version but offers different characters to choose from. The player's character choice matters as each one has unique attributes such as reload time and damage before dying. In Boss Mode, you can fight one of four boss monsters or all of them in a row.