Based on a novel by Lois Duncan, Hotel for Dogs is the story of two orphaned siblings, Andi (Emma Roberts) and Bruce (Jake T Austin). Andi and Bruce have great difficulty finding foster parents who are willing to look after them both. Their current foster parents, the fifth set in three years, are self-absorbed, would-be rock stars, Lois (Lisa Kudrow) and Carl (Kevin Dillon). Lois and Karl have taken in Andi and Bruce only because of the income paid to foster parents.

Andi and Bruce often find themselves in trouble with the law as they think of devious ways to make money. They have a very caring social worker, Bernie (Don Cheadle), who always bails them out of trouble. They also have adopted a dog, Friday, which isn’t allowed to live with them, but they manage to keep his existence a secret.

On one occasion, while trying to run from the police, Andi and Bruce follow Friday into a condemned building. Here they are surprised to find two more abandoned dogs. They decide to clean the place up and look after all three dogs. Andi is then persuaded by Dave (Johnny Simmons), who works at the local pet shop, to take three more dogs because he can’t keep them at the shop anymore. One thing leads to another. Before long, there are lots of dogs living there, causing mayhem and mess. The ingenious Bruce, however, makes clever gadgets that help with feeding, cleaning, exercising and entertaining the dogs. Things go wrong when the local dogcatchers discover where all their dogs have gone.