Jack (GEORGE CLOONEY) has spent too many years as a contract assassin, either killing people himself or making guns for other assassins to shoot people. He wants out of the life and craves seclusion. When someone orders a hit on him, Jack takes the opportunity to meet with his enigmatic boss, Pavel (JOHAN LEYSEN), in Rome. There, Pavel arranges for Jack to hide out in a small, secluded Italian town.
When Jack gets to the town, though, he doesn't like the looks of it. So, he decides to pick his own hiding spot in nearby Castel del Monte. There, he meets two people. The first is Father Benedetto (PAOLO BONACELLI), an inquisitive priest who wants only to discuss sin and redemption. The second is a good-hearted prostitute named Clara (VIOLANTE PLACIDO) who wants to start a new life with him.
Pavel, though, has one more job for him. Jack is to construct a special rifle for a female assassin named Mathilde (THEKLA REUTEN). Jack tells him that this will be his final job, as he has become paranoid of everyone around him. His suspicions eventually prove true when two of the characters turn against him, leading to a climactic game of cat and mouse.