Trong phim "Cặp Đôi Hoàn Cảnh", một nữ cảnh sát nghiêm nghị và quy tắc lại nhận phải một nhiệm vụ bảo vệ người vợ cũ vô cùng quyến rũ và gợi cảm của một ông trùm ma túy, chạy trốn khắp nơi trên Texas khỏi nòng súng của cả những kẻ sát nhân lẫn những tên cảnh sát "giang hồ".
Rose Cooper is a San Antonio Police Department officer whose work ethic is too intense. Cooper's name has become a verb synonymous with screw-ups, following incidents such as overreacting when the mayor's son yells "Shotgun!", tasing him and setting him on fire when his alcoholic drink spills.
Captain Emmett informs Cooper that she will escort Deputy US Marshal Jackson, protecting Felipe Riva and his wife Daniella. Riva must go to Dallas to testify against notorious cartel leader Vincente Cortez. Cooper and Jackson arrive at the Riva home, when two masked men shoot and kill Jackson and Felipe while Cooper and Daniella are upstairs packing. Daniella grabs one suitcase, and the ladies flee in Riva's car. When Cooper pulls the car over, Daniella grabs her bag to walk away on her own, leading Cooper to handcuff herself to Daniella to make sure she's close to her.
The ladies are found by Cooper's fellow officers Dixon and Hauser. When Cooper recognizes a tattoo that reveals the officers as the assassins, the ladies pretend that Daniella is having her period so they can go to the bathroom and make their escape. They intend to proceed to Dallas, where Daniella can testify against Cortez.
The ladies learn that Cooper is now considered a fugitive that is fleeing with Daniella. A truck plows into the car, spraying hidden cocaine everywhere. Cooper becomes high on cocaine and gets the truck driver to drive them to a nearby clothing store. Dixon and Hauser show up, leading the ladies to stow away in a trailer hooked to a pickup truck. There, Cooper learns that Daniella's luggage contains many pairs of shoes, studded with fake diamonds, that were gifts from her now dead brother. After the vehicle is parked, Cooper searches the truck for keys, when the owner, Red, reappears with a gun. Daniella initially escapes, but comes back for Cooper and pretends to be her lesbian lover. She starts to uncomfortably grope and make out with Cooper, briefly distracting Red until he accidentally shoots off his finger. Cooper and Daniella grab another pickup truck and drive away.
On the road, the ladies continue bonding, with Cooper admitting that her by-the-books nature has made it difficult to find a man. They are surprised to find a man sleeping in the back of the truck. Randy is a felon with an ankle bracelet due to viciously assaulting his sisters' abusive boyfriends. Cooper agrees to take off the bracelet in return for Randy's help. Daniella is pleased to see Randy flirting with Cooper.
Stopping at a hotel for the night, Cooper cuffs Daniella to the bedpost while she goes to Randy's room to get food. She walks in on him naked and eventually succumbs to his charms and kisses him. Cooper goes back to her room to find Daniella aiming Cooper's gun at her, upset that Cooper's notes reveal her doubts that Daniella would be smart enough to properly testify. Daniella explains that her bag of shoes have $4 million in real diamonds, Riva's money laundering method. When Dixon and Hauser appear and shoot at the ladies, Randy attacks Hauser, allowing the ladies to run.
The ladies escape on a tour bus, followed by the crooked cops as well as two of Cortez' thugs. The ladies use the bus to bump the cop's car off the road. Daniella punches Cooper's lights out – when she comes to, Cooper sees Daniella working with the thugs. She learns that Daniella is working with them as part of her plan to murder Cortez for killing Daniella's brother. She plans to get him at his daughter's Quinceañera. Daniella had arranged for the thugs to kidnap her but did not plan for her husband to die. She escapes, leaving Cooper to bring in Dixon and Hauser, earning praise despite failing the rest of the mission.
Cooper sneaks into the Quinceañera as a man to get close to Daniella. She tries to get her to wear a wire so that they can get Cortez to confess to her brother's murder, but a woman walking into the bathroom mistakes Cooper for a pervert and throws her out. She gets back into the party, running into Emmett and learning that he is working for Cortez. He pulls a gun on her, but Cooper pours alcohol on him and tases him so he catches fire.
Daniella corners Cortez and reveals her intentions to kill him. Cooper arrives and stops Daniella, when Cortez draws a gun and Cooper shoots him dead. Daniella is angry at Cooper for stealing her revenge, until she sees that Cooper took a bullet for her in the arm.
Three months later, Cooper picks Daniella up from prison after an obstruction of justice conviction. Cooper is no longer a laughingstock and is praised for taking down Cortez. Outside, she presents Daniella with her shoes. They leave together, and Daniella sees that Cooper brought Randy along with her.
