In the heart of New York City, Max, a pampered terrier, enjoys a comfortable life with his owner Katie and believes he is the center of her world. His perfect life takes an unexpected turn when Katie brings home Duke, an enormous and boisterous mongrel from the pound. Initially, Max feels displaced and jealous, leading to friction between the two dogs. Unaccustomed to sharing his owner's affection, Max instinctively schemes to regain his status as Katie's sole companion. However, during a walk with their dog-walker, Max and Duke find themselves abandoned and without their collars, making them vulnerable in the urban jungle.

Their journey takes a perilous turn when they run into a gang of alley cats, leading to a chase that leaves them lost in the labyrinthine streets of the city. The two end up being captured by Animal Control, setting off an unlikely chain of events. Meanwhile, a group of Max's pet friends—led by Gidget, a spirited Pomeranian who has a crush on Max—learns of his predicament. Determined to rescue him, Gidget and the gang venture out on a daring mission. Simultaneously, Max and Duke's struggle to get back home teaches them to put their differences aside and work together in order to survive the dangers of the city and find their way back to Katie.