The flu season has come about, and it's Dr. Mario's duty to use his Megavitamins to heal the people of the land. However, Wario, wanting to have the fame that Mario has, attempts to steal the Megavitamins, but to no avail. Afterwards, Mad Scienstein and Rudy the clown (from Wario Land 3) steal the Megavitamins, and both Dr. Mario and Wario go after him. 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, you may accidentally bump into a creature, who gets angry and retaliates. Dr. Mario and Wario follow Mad Scienstein to Rudy's castle, where you must fight Rudy to take back the vitamins. If you complete the game on normal or hard mode without continuing, you will play one more stage after defeating Rudy. The opponent is Metal Mario if you used Wario and Vampire Wario if you used Dr. Mario.