Manny moves to a new school and wishes for more friends. He finds a special collar and puts it on his dog Rufus, transforming it into a boy. After Rufus joins Manny's school, his instant popularity tests the bonds of their friendship.

Rufus 2 is the sequel to the Nickelodeon Original Movie Rufus. Leading stars include Nickelodeon stars Jace Norman (Henry Danger), Jade Pettyjohn (School of Rock), and Haley Tju (Bella and the Bulldogs).