In Cuphead, run-and-gun levels are interspersed with boss battles. In one of the four worlds, each faces the Devil in their final conflict. Except for the final two bosses, which don't have an easy level, every boss encounter has three difficulty settings: easy, regular, and hard. You must defeat a boss in normal mode in order to play and unlock expert mode for a level. While some boss battles take place in side-scrolling shooters, the majority are on land. Role-playing and branching stages are included.

The player's character has endless lives and retains all of his or her gear. For coins found in levels and worlds, players can purchase Charms, weapons, and abilities at Porkrind's Emporium, an in-game store. Slapping pink-marked things will strengthen the player's supermeter. Super metres, which are five cards, are charged by attack effects and charms. One card is required for a weapon-specific boosted attack. A fully charged Super Clock is needed for Super Arts, which entirely drain it. Entering a mausoleum and preventing a funeral procession from reaching an urn in the center of the screen is how the first three Super Arts are obtained.

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