FBI Special Agent Sarah Ashburn (Sandra Bullock) is a very skilled and effective investigator in New York City, but is despised by her fellow agents for her arrogance and condescending attitude. In Boston, she meets Shannon Mullins (Melissa McCarthy), a skilled but foulmouthed and rebellious police officer with the Boston Police Department. Ashburn’s by-the-book philosophy clashes with Mullins’ rugged and violent style of police work. Under pressure from Hale (Demián Bichir), her FBI boss, Ashburn reluctantly agrees to team up with Mullins.
Ashburn and Mullins tail a local nightclub owner named Hank LeSoire (Adam Ray) to his place of business known as Club Ekko and successfully place a bug on his cell phone in an effort to get information on a drug lord, Simon Larkin. As they leave the club, Ashburn and Mullins are confronted by DEA agents Craig (Dan Bakkedahl) and Adam (Taran Killam), who have been working the Larkin case for several months and are worried that their case will be compromised.