Siblings Andi (Emma Roberts) and Bruce (Jake T. Austin) are orphans, and they live with wannabe rock-star foster parents Lois and Carl Scudder (Lisa Kudrow and Kevin Dillon). Due to the foster parents awful treatment, the kids and their beloved dog Friday (who is hidden from the foster parents) spend their days on the streets. To get money for food for themselves and the dog they deceive a pawn shop, but are caught. Their social worker Bernie (Don Cheadle) reprimands them, but helps them to minimize the damage.
One day while out on the streets as usual, they witness a store being robbed. The police seeing the two kids standing nearby accuse them as being the robbers and here starts a silly chase all over town. The kids eventually hide in an old abandoned hotel but are spooked when they hear footsteps and chairs falling over. They discover the hotel is occupied by two dogs.
The following day the kids gather up all the food from their foster parents' pantry and refrigerator and secretly take the food to the hotel for the dogs. That's when they get the idea to turn the hotel into a home for the three dogs and any other strays they can find. They are joined by a boy named Dave (Johnny Simmons), a girl named Heather (Kyla Pratt), (both of whom work at a pet store) and later by a kid who lives nearby named Mark (Troy Gentile).
The kids rescue about 20 or so dogs. Bruce invents and constructs many ingenious machines using parts he steals from his foster parents, to help feed the dogs and provide sanitary facilities, exercise and entertainment for them. The dogs are quick in learning how to use the machines.
Later on Bernie announces to them they can move from the foster home they hate to a new one that is a few hours away. Even though this may be their last chance to be placed in a foster home together, they decline as they care too much about the dogs to abandon them, but they cannot tell Bernie this reason because they might be forbidden to continue their care for the dogs.
One night while Andi and Dave are at a party (which turns into a disaster when Andi ends up getting punch on her dress, causing her to leave the party in tears) and Bruce is at his foster parents being reprimanded for a hair dryer he stole from them, the machines fail and the dogs go wild and cause so much noise that the police are called. The dogs are taken to a pound and Bruce and Andi's foster parents kick them out for stealing. As predicted, they are sent to separate foster homes. The pound prepares to euthanize the dogs, but Friday escapes and finds Dave. The two reunite all of the kids and they decide to save the dogs despite the fact that they are going to get in big trouble. They break the dogs out of the pound and try to lead them over the county line (Bruce tempting them to follow the van with sausages) to an animal shelter that has a no kill policy, but as the dogs get close to the hotel, they make a bee line there instead as that is their 'home'. The kids and a massive crowd of people follow.
The police call Animal Control who tries to take them back,. Bernie having seen what the kids did, makes a speech in favor of the dogs for the kids rescued so many strays and gave them a home which is something he had been trying to do with the kids he dealt with. (When he introduces the two twin dogs, Viola and Sebastian, this makes reference to the play, "Twelfth Night". The characters Viola and Sebastian are twins in the play. And the dogs Romeo and Juliet are mates).
With donations from the people of the city, the hotel is fixed up and turned into an actual hotel for dogs. The kids all work there. Lois and Carl Scudder are 'howling' good entertainment for the dogs in the lounge and Bernie and his wife end up adopting Andi, Bruce, and Friday.