Santa Mira was a location featured in the episode Max Out. It was during Spring Break while on his way to Bellwood to be with his family Ken Tennysons' car: "The Awesomemobile" broke down in Santa Mira and was waiting for it to be repaired. It was during his stay in town that Ken was captured by the DNAliens in order to lure his grandfather Max Tennyson there in order to kill him. Having caught on to the ruse employed by the converted people of Santa Mira, Max set out to find his eldest grandchild himself; traveling to the Hatchery in order to save him from the Highbreeds control. Also concerned about her older brother, Gwen Tennyson, Kevin, and Ben made the journey to Santa Mira themselves to find out where he was.
At the end of the episode, Ben discovers that the Highbreed plan to use the town as a hatchery for their Xenocytes in order to spread them across the country and turn every human into DNAliens loyal to them. Max Tennyson then removed the focusing lens to his portable Null Void Projector in order to turn it into a makeshift bomb while Gwen shielded Kevin, Ken, and Ben as they watched helplessly as Max activated the Null Void Projector: Destroying all of Santa Mira in the process, along with killing all Highbreed and DNAliens within the city save for Ben who was determined to protect the Earth believing his grandpa to be dead.