Struggling to unite the Wild and Leashed Packs for mutual safety after a violent attack, Lucky is cast out by a ruthless Alpha and encounters treacherous elements in the forest and ruined city, which is rapidly enveloped by a poisonous black cloud.

The boy knows that times are tough for his family. Every night, his father goes out hunting with their great coon dog, Sounder, to try to put food on the table. But even with the little they bring back, there is still never enough for the family to eat. When the boy awakens one morning to a sweet-smelling ham on the table, it seems like a blessing. But soon, the sheriff and his deputies come to the house and take the boy’s father away in handcuffs....

When all humans in his world disappear, Max, a yellow Labrador Retriever, searches for Madame Curie who, he knows, will help find his people but as he and friends Rocky and Gizmo search, they face angry wolves, a gang of subway rats, and the Corporation, a supposed "perfect" society for dogs.