Wario's temper tantrum has led him on a wild adventure, taking him to Dr. Crygor's lab where he discovers a mysterious device that creates hundreds of Game Boy Advance systems with no buttons and an addictive tilt control. Wario soon realizes that this is the key to his next big fortune, and thus WarioWare Twisted! was born.
The game follows Wario as he navigates through stages filled with over two hundred five-second games, each with a unique description and time limit to complete. The player must figure out what to do with a brief instruction like "Play!", "Avoid!" or "Digest!". With four lives at his disposal, Wario must pass enough games to progress, but failure will result in losing one of his lives. As the player progresses, the games become increasingly faster and more challenging.
The game features five distinct character stages, each with a unique theme: Mona's spin-based games, Jimmy T.'s rhythm-based games, Kat and Ana's A-button focused games, Dr. Crygor's gravity-altering games, and 9-Volt and 18-Volt's Nintendo-style games that incorporate various gameplay styles. Additionally, WarioWare Twisted! boasts a vast array of novelty unlockables to collect, including bonus toys and prizes.