In honor of Twayne's 10-year anniversary of running the D.O.I., Callie and the crew throw him a Roast. But when Mark's attempt at edgy humor goes too far, Twayne quits, leaving Mark in charge. Before his first day as boss is up, Mark makes a management mistake so catastrophic that it almost destroys New York City.
An ant-sized arsonist named Jerry flees Mark's custody, escaping up Twayne's nostril. A miniaturized Leonard, Grimes and Mark must track Jerry through Twayne's body to bring him to justice.
With Mark working all the time, Randall feels neglected, so he decides that they should spend more time together to decide if they should stay roommates. And Grimes's Mummy (Christine Baranski) returns from the dead, only to find fault with everything Grimes is doing.
Callie reveals to Mark that she's been sleeping with other guys. So when Mark's college girlfriend (Jenny Slate) shows up, he decides to put his newly "open relationship" with Callie to the test.