The Brothers Bloom start their adventures in confidence tricks as young children; Stephen dreams up elaborate scenarios and his younger brother, Bloom, creates trust with the marks. The brothers’ successful cons and the fiercely protective nature of Stephen has the children rejected from foster homes throughout their childhood.
25 years later the brothers are celebrating the end of another con. At the party Bloom realizes that Stephen controls everything in their lives. Bloom decides to quit and move to Montenegro. Three months later Stephen finds Bloom and convinces him to execute one final con masquerading as antique dealers with Bang Bang, a Japanese explosives expert. The con is on Penelope Stamp, a rich socially-isolated New Jersey heiress. To meet, Bloom stages a car accident but during the accident she seizures and is taken to the hospital.
Penelope is discharged and reveals to Bloom that she was alone for most of her life. Bloom hints that he is leaving the country tomorrow. Next morning at the harbor Penelope arrives to accompany Bloom to Greece. Maximillen, a Belgian hired by Stephen, tells Penelope that the Brothers Bloom are in fact antique smugglers. Enchanted, Penelope decides to become a smuggler. Maximillen, as instructed by Stephen, offers Penelope a smuggling job of retrieving a book from a museum in Prague. Penelope convinces the Brothers to travel to Prague, unaware it is staged. On the train Penelope expresses affection for Bloom.
In Prague they meet with Maximillen to plan stealing the book. According to Stephen's plan, Maximillen cons Penelope out of a million dollars and escapes. Penelope decides to steal the book anyway. The plan is to place explosives in Prague Castle to set off the fire alarm, evacuating the building. Instead Penelope accidentally blows up the entire tower, resulting in the military arriving; Penelope, unaware of the military, enters the museum. She retrieves the book and during escape through a ventilation shaft, it gives out dropping her into a room filled with soldiers. Penelope convinces the chief of police to let her go.
While in their hotel's bar, Bloom is visited by the former mentor of the Brothers, and current enemy, Diamond Dog. He warns Bloom that Stephen will not be around forever, Bloom should join him. Bloom turns down the offer as Stephen arrives; Stephen stabs Diamond Dog in the hand with a broken bottle, telling him to "stay away."
In Mexico Bloom tells Penelope they are con men which was anticipated by Stephen. The brothers fight and a gun accidentally discharges, Stephen is shot. Penelope checks out the wound, realizes that it is fake blood, and leaves with a broken heart. Bloom punches Stephen and leaves for Montenegro. Three months later, Penelope visits Bloom to become a con artist. Not able to deny his love for her, he meets with Stephen to set up one final con.
The brothers set off to St. Petersburg where they must sell the book to Diamond Dog. They are ambushed by Diamond Dog's gang while headed to the exchange. Stephen is kidnapped and held for $1.75 million. Bloom suspects this is just another con by Stephen; Penelope, just in case, wires the money by her bank account to the mobsters. Before the exchange, Bang Bang decides to leave and makes her exit by car bomb; leaving Penelope and Bloom uncertain she faked her death.
Alone Bloom goes into the theater for the exchange. Bloom finds Stephen tied up and beaten. A hitman attacks them and Stephen gets shot and collapses on the floor. Bloom asks Stephen whether this was real, or just the "perfect con." Stephen gets up and assures Bloom that he is fine. Stephen tells Bloom to leave St. Petersburg forever with Penelope and that they will meet again.
Bloom wakes up in the car and discovers that Stephen's blood stain on his shirt has changed in color from red to brown, indicting that the blood was not fake but real. Realizing that Stephen has died, Bloom breaks down on the side of the road while Penelope tries to comfort him. As they are leaving, Bloom recalls what Stephen had said earlier, "The perfect con is one where everyone involved gets just the thing they wanted." For Penelope and Bloom, what they wanted was life with each other, while for Stephen it was to write a con so perfect it became real: thus,Stephen pulls the "perfect con", Diamond Dog really gets revenge, and Bloom and Penelope drive off.
