As Andi (Emma Roberts) and Bruce's mischievous antics culminate in an unexpected police encounter, they find themselves at a local station where their social worker, Bernie Wilkins, shows a caring yet firm disposition. He advises them against seeking trouble as a means to escape from their indifferent foster parents, Lois and Carl Scudder. The siblings, along with their devoted dog, Friday, feel the weight of neglect from the Scudders.
The following morning, driven by hunger, Friday ventures out in search of food and unfortunately gets captured by Animal Control. Determined to reunite with their cherished pet, Andi and Bruce head to a pet shop, where they are aided by the compassionate Dave and Heather. They recommend that the siblings check the pound, which leads them to discover Friday is indeed held there. However, without an adult present, they can't reclaim him, pushing Andi and Bruce to use their wits and resources to bribe their way to Friday's freedom.
On their way home, they unwittingly escape a crime scene and stumble upon an abandoned hotel that offers them refuge for the night. Inside, they encounter new furry friends—a small Boston Terrier and a big English Mastiff, whom they name Georgia and Lenny. Andi decides to leave Friday at the hotel, reassured that he'll be safe with his newfound companions.
While Bruce stays behind to hush the dogs, Andi sets out to gather food. She crosses paths with Dave and Heather again and invents an elaborate story about their parents' love for rescuing dogs, which leads Dave to insist she take in even more strays. Reluctantly, Andi agrees, leading to a situation where the number of dogs in their care balloons to six. Together with Bruce and their friends, they embark on a mission to transform the decrepit hotel into a haven for their furry pals.
Excitement fills the air when Andi agrees to attend a party with Dave, while Bruce faces scrutiny from Lois and Carl following a theft. To add to the drama, Andi encounters Jason, an old acquaintance, who reveals that both she and Bruce share an orphan bond. This revelation drives Bruce to flee from their foster situation, only to find chaos at the hotel as authorities round up the dogs, including Friday. When both siblings are taken in by the authorities and separated into different foster homes due to Lois and Carl's refusal to help, it's Bernie who steps in, trying to navigate the complex situation.
In a race against time, with the dogs facing imminent euthanasia, Friday proves his cleverness by escaping and leading Dave, Heather, and Mark back to help Andi and Bruce. Bernie, on his own quest for the truth about the hotel, meets Harley, a dog that had managed to evade capture, deepening his understanding of the children's connection to their extraordinary lifestyle.
Desperate to save their beloved dogs, Andi and Bruce hatch a plan to break into the pound. They aim to guide their canine companions to safety across the county line, but the dogs' instincts pull them back to the hotel, which they view as their home. This unusual scene catches the attention of onlookers and the media, ultimately drawing authorities as well. Just as hope begins to fade, Bernie arrives, captivating everyone with a heartfelt recount of Bruce and Andi's unbreakable bond with their dogs, beautifully documented in a registration book. The emotional narrative sways the officials, allowing the children to keep their furry friends.
With the hotel reborn as the "Hotel For Dogs," a shelter for strays and a boarding house for pet owners, Andi, Bruce, and Friday find solace and love at last, embraced by Bernie and his wife, who decide to adopt them into their family.
