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The world is again rebuilding after the events of Universal Tour. To clean up the mess quicker, Scumlabs invent a time machine to send people back in time to fix the mess without having to do it in the present. Unfortunately, the monsters, who have somehow made it back to Earth (joined by another monster named Harley, a warthog monster), appear and run into the machine. They begin terrorizing the past, present, and future, messing up the time stream. Later, a UFO-like craft is created to stop the monsters but it fails. Eventually, the monsters are finally stopped for good.
In Campaign Mode, each timezone consists of four stages. The first three consists of traditional Rampage gameplay, in that you must destroy all the buildings in each city while avoiding attacks from enemy forces. Campaign Mode is only playable with one player, but the CPU will randomly select two other monsters to oppose you in that timezone. After each city is destroyed, all three monsters are awarded stars for inflicting the most damage on buildings, people, and each other.
The fourth stage is a multiplayer minigame that varies with each timezone, usually as a parody of games such as Asteroids or Breakout. In Campaign Mode, the player must win these minigames in order to continue with the main game. The stars earned in the Rampage stages are also translated into extra points for the minigames, making it important to earn as many as possible to increase the chances of winning.