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"From the creators of Despicable Me"
"They still have their secrets."
Sometime after the events of the first film, Max and Duke's owner, Katie, gets married to a guy named Chuck and has a son, Liam, whom Max disapproves of at first due to his rough play but eventually softens up to him. Later, Max's overprotective feelings for Liam develop into an itch which prompts Katie to get him a dog cone from the veterinarian in an effort to lower his symptoms. Max's luck changes when Duke reveals that the family is going on a road trip outside of the city.
When Max and Duke's family reaches a farm owned by Chuck's uncle, Max grows unaccustomed to the farm's ways, including local sheepdog Rooster. After an incident with the farm's sheep, Rooster takes Max out to find one of the missing sheep that ran away. Rooster's teaching and encouragement to Max about acting unafraid prompts Max to successfully retrieve the sheep. Rooster allows Max to stay with him overnight as a result. Before departure, Rooster also gives Max one of his handkerchiefs as a souvenir.
Before Max left, he had entrusted his favorite toy, Busy Bee, to Gidget. Unfortunately, Gidget loses Busy Bee in a cat-infested apartment owned by a cat lady. She receives cat lessons from Chloe, Mel, Buddy, and Sweet Pea in order to sneak in the apartment easier. With the help of Norman, she successfully retrieves Busy Bee and unintentionally gets hailed as the "queen of cats".
Meanwhile, Chloe and Snowball meet Shih Tzu Daisy, who explains that she needs Snowball, who dreams of being a superhero, to assist her with rescuing a White tiger cub named Hu. While on flight back to the city, Daisy encountered him being held captive by an abusive circus owner named Sergei. Daisy and Snowball sneak in and find the circus Hu is in. With much difficulty from Sergei's black wolves, they free Hu from the circus. However, in the heat of the escape, Daisy accidentally drops her flower clip, which the wolves use to track her down.
She and Snowball take him to Pops' apartment first. Pops reluctantly lets Hu live there at first, but due to his destruction of the apartment afterwards, Hu is kicked out and relocated in Max and Duke's apartment. Around the same time, the family returns from the trip. Sergei and his wolves track Daisy down and capture both Hu and Daisy. Sergei escapes in his train moving for the circus in which Snowball, Max, and Norman pursue while contacting Gidget for assistance in the chase. Gidget and the cats take their owner off in her car, in pursuit of the train.
Max and Snowball defeat the wolves and Sergei's pet monkey, while freeing Hu and Daisy respectively. Max, using his newfound bravery Rooster gave him, successfully infiltrates the train locomotive Sergei is in. The rest of the animals go and kick him out of the train. But before they are shot by Sergei, Gidget, along with the cat lady, Chloe, Mel, Buddy, Duke, and Sweet Pea knock him out with her car and offers the animals a ride back home. Life resumes normally, with Max and Duke's family saying goodbye to Liam as he enters his first day of preschool while Hu takes up residence in his new home with the cat lady and Snowball becomes New York City's local superhero.