Dr. Mario 64 is a Mario tile-matching action puzzle video game developed and published by Nintendo for the Nintendo 64. The game was released in North America on April 8, 2001.

The flu season has come about, and it is Dr. Mario's duty to use his Megavitamins to heal the people of the land. However, Wario, wanting to sell the pills to get rich, attempts to steal the Megavitamins, but to no avail. Afterwards, Mad Scienstein (from Kaeru no Tame ni Kane wa Naru) and Rudy the Clown (from Wario Land 3) steal the Megavitamins, and both Dr. Mario and Wario give chase. Throughout their adventure, both of them meet up with many creatures from Wario Land 3. Most of the time the fights that emerge are really misunderstandings; for example, the player may accidentally bump into a creature, who gets angry and retaliates. Dr. Mario and Wario follow Mad Scienstein to Rudy's castle, where they fight Rudy to take back the vitamins. If the game is completed on Normal or Hard mode without using a continue, one last battle occurs after defeating Rudy; the opponent is Metal Mario for Wario and Vampire Wario for Dr. Mario.