The series is set in the Big City, a city modeled after New York City. The story follows Blythe Baxter and her father as they move into a Big City apartment above the Littlest Pet Shop – a day-camp for pets of all kinds. Her real adventure begins when she discovers that she alone can miraculously understand and talk to all of the pets. Along the way, she and the pets go on several adventures together but when the pet shop is about to close due to a bigger pet shop driving it out of business, managed by the Biskit Twins. Having no choice, the pets turn to Blythe to help them save it from closing down.
