Twayne quits after getting roasted at his DOI 10-year anniversary party, leaving Mark in charge. Consequently, Mark almost destroys New York City.
When a Lilliputian arsonist escapes custody and hides in Twayne's nose, a miniaturized Leonard, Grimes and Mark enter Twayne's body to bring the fire starter to justice.
Grimes' judgmental mother rises from the dead, only to criticize everything the DOI's top cop does. A neglected Randall tries to decide if he and Mark will stay roommates.
Twayne throws a cruise ship party, and Mark Lilly is the only one who can save his friend Randall from a horrific plant species infection.