When their owners leave them behind on a ranch in California, three pets -- Chance, a young dog unfamiliar with the world; Shadow, an aging, wise dog; and Sassy, a snobby cat -- set out to find them. Their journey takes them across the Sierra Nevada mountains, through harsh wilderness, and down a waterfall. Along the way, they encounter various dangers and obstacles, but their determination and love for their owners keep them going.

Homeward Bound II: Lost in San Francisco follows two pets, a cat and a dog, along with their human companion as they get separated from their family and must navigate the bustling city to find their way back home. Along the way, they encounter various challenges and form new friendships.