"South of the Border" chronicles the adventures of a pampered Beverly Hills chihuahua named Chloe (Barrymore) accustomed to riding in a purse. While on vacation in Mexico, she gets lost and must rely on her friends to help her get back home.

Garcia is playing a German shepherd who was kicked off the police force because he lost his sense of smell and has now given up on life. Hayek is Chloe's spirit guide who helps her find her true heritage.

Lopez is Papi, a macho romantic Chihuahua who will do anything for the love of Chloe.