The game features Mario as he tries to kill viruses by matching a certain number of pill of the same color together. Other characters also include Wario and Metal Mario, the later being from Super Mario 64 and the former from multiple other Mario video games. The gameplay is similar to the previous Dr. Mario games, which is understandable. Despite having the same classic gameplay that made the original so popular, it was critically a failure.
Vampire Wario, a variation of the regular Wario, is an unlockable character. To obtain the character, the player will have to play and defeat single player mode on normal or higher without losing once. Metal Mario is also unlockable, and to unlock him Dr. Mario will have to do the same tactic as he did with Vampire Wario, though the player will have to use Wario to beat the game.