South Park: Let's Go Tower Defense Play! — Cartman runs to Stan's house to warn him that "terrible creatures" are attacking South Park. The two are able to defend the house from an army of red children and cows before taking Kyle and running to their school. They manage to secure the area again, but Cartman receives a call from Kenny, who has been attacked. Helping Kenny fight off another horde of enemies, the boys come to the conclusion that the culprit of the unrest can only be an evil supervillain: Professor Chaos.
Like other tower defense games, players must destroy waves of enemies using towers strategically placed around the path. Additionally, players can directly control the character to directly attack enemies and collect dropped coins to buy and build more towers. In a single player game, the player switches between each character, while in a multiplayer game, characters are assigned to each player.