Larry Daley is a divorced father who can't seem to keep a job for more than a week. As a last resort, Larry applies for a job as a night shift security guard at the American Museum of Natural History. However, a seemingly easy job turns out to be an adventure when he finds that an ancient curse causes the "inhabitants" of the museum to come to life at night.

Terrier Max is coping with some major life changes. His owner is now married and has a toddler, Liam. Max is so worried about protecting the boy that he develops a nervous tic. On a family trip to a farm, Max and Duke encounter many creatures who elevates Max's anxiety. Luckily, Max gets some guidance from veteran farm dog Rooster, who pushes Max to ditch his neuroses, find his inner alpha, and give Liam a little more freedom. Can Max and the gang...