Puss discovers the mythical city of San Lorenzo but is soon needed to guard the city from thieves after he unknowingly reverses an ancient protective enchantment placed on the city.

Puss unknowingly endangers a group of orphans after he gives them magic sugar. Puss must cure the orphans, but the only remedy is shielded by a powerful sphinx who challenges him with befuddling riddles.

San Lorenzo's treasure is threatened by Toby's ninja brothers, who seek to get him to steal it for them. Toby is faced with a difficult situation where he is forced to choose between his family and his friendship with Puss.

Puss must rescue Artephius after he is kidnapped by The Duchess, who is hell-bent on world domination. The Duchess wants to increase her strength by tapping into the power of sorcerers.

Puss is deceived into performing a mission to rescue a princess with his old friend, Jack Sprat. However, the situation soon turns hazardous when the duo are attacked by a scary monster.

Dulcinea and Puss undertake an adventure to locate the Fountain of Youth. Puss's old mentor, El Guante Blanco, staggers into San Lorenzo and wishes assistance from his pupil.