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|Adam Sandler||Nick Spitz|
|Jennifer Aniston||Audrey Spitz|
|Luke Evans||Charles Cavendish|
|Terence Stamp||Malcolm Quince|
|Gemma Arterton||Grace Ballard|
|David Walliams||Tobey Quince|
|Dany Boon||Inspector de la Croix|
|John Kani||Colonel Ulenga|
|Ólafur Darri Ólafsson||Sergei|
|Luis Gerardo Méndez||Juan Carlos Rivera|
|Shioli Kutsuna||Suzi Nakamura|
"First class problems. Second class detectives."
Nick Spitz (Adam Sandler) is a New York police officer, and his wife Audrey (Jennifer Aniston) is a hairdresser. Audrey wants to visit Europe, as Nick had promised at their wedding, but thinks they never will. After their 15th-anniversary dinner, Audrey confronts Nick, who lies that he has in fact booked the trip, and they set off to Europe. On the plane, Audrey meets billionaire Charles Cavendish, who invites the couple to join him on his family yacht for a party celebrating his elderly uncle's upcoming wedding to Charles' former fianceé. After seeing how crowded their previously planned bus tour would be, Nick agrees.
Aboard the yacht, Nick and Audrey meet Cavendish’s ex-fiancée Suzi, his cousin Tobey, actress Grace Ballard, Colonel Ulenga, his bodyguard Sergei, the Maharaja Vikram of Mumbai, race car driver Juan Carlos Rivera, and their host Malcolm Quince, Cavendish’s uncle. Quince announces that his new wife Suzi will be the only one to receive his inheritance, believing the others only feign interest in him because of his money. Before he can sign his new will, the lights go out and come back on to reveal Quince dead, stabbed by his own dagger.
Nick, who has lied to Audrey about being an NYPD detective, orders the room locked, and the guests return to their rooms. Later that night, the guests find Tobey, Quince’s only son, dead from an apparent suicide. Upon arriving in Monte Carlo, the guests are questioned by Inspector Laurent Delacroix, who believes Nick and Audrey guilty of the murders.
At the Monaco Grand Prix, Nick and Audrey question the guests. That night, Sergei summons them to his room, where he reveals Quince had married the Colonel’s fianceé while the Colonel was in a coma, which ended with her death and a child who was allegedly stillborn. The couple hide when someone knocks on the door, and come out to find Sergei has been murdered. While fleeing, they see on the news that Delacroix has issued a warrant for their arrest. Audrey is furious to learn Nick is not actually a detective and lied about booking the trip in advance, and she leaves with Cavendish.
Nick follows Suzi to a library where he finds Audrey, who reveals Cavendish is in the building as well. They realize Cavendish and Suzi are still in love and, presumably, the murderers. The couple are forced to flee from a hidden gunman and meet Rivera, and are confronted by Suzi, who is killed by the masked killer. Nick and Audrey go to Quince’s mansion to confront Cavendish, but find him dead by poisoning.
The couple summon Delacroix and the remaining guests Ulenga, Grace, Vikram, and Rivera, who all have alibis. Nick and Audrey deduce that Grace is the murderer; she was helped by Tobey, then killed him. Grace reveals that she is Quince’s child that “died” and that his money truly belongs to her. Though Grace denies being the killer, Audrey proves her guilt and she is arrested.
While celebrating, Nick and Audrey learn that Grace had another alibi and there must be another killer. They realize Rivera is the second murderer, who blamed Quince for an accident his father had where he had lost both of his legs. Rivera holds Delacroix hostage and leads Nick and Audrey in a car chase, but they force his car to crash and rescue Delacroix. Rivera holds them all at gunpoint, but is killed by the chaotic tour bus, which Nick and Audrey would have initially boarded earlier.
Delacroix thanks the couple and offers to help get Nick promoted to detective back home. The movie ends with Nick and Audrey continuing their vacation aboard the fabled Orient Express courtesy of Interpol.