Anchor plot: Philippe Letzger (Philippe Lefebvre) is the host of It's Tissue Time!, an exploitation television game show where contestants are made to cry. The show's audiences are warmed up by one of Letzger's assistants, Bastien (Guillaume Canet), an ambitious young man who provides Letzger with good ideas for the show, for which his boss eagerly takes credit. Bastien tolerates Letzger's antics in order to work with Jean-Louis Broustal (François Berléand), the show's sophisticated producer whom he admires. Bastien's girlfriend, Fabienne (Clotilde Courau), is frustrated by his worship of the suave producer. Bastien is equally frustrated when he finds out that the blonde he is attracted to at the office is in fact Broustal's young wife, Clara (Diane Kruger).
One day, Broustal begins to take interest in Bastien's ideas for the show, and invites him to spend the weekend with him and his wife at their country estate to work on a concept for a new show called Proof in Pictures. When they arrive, Clara quickly seduces Bastien, but Broustal does not seem to care. During the weekend, Broustal tells the young man that he can make him a television star, but the couple's motives seem strange, and possibly sinister.

Plot A: Leon Phelps (also known as the "Ladies Man") was a Saturday Night Live character played by Tim Meadows during the 1990s.  The sketch was that of a broadcast program in which Phelps, a young, suave black man, would give dubious romantic advice and lovemaking tips.  The Ladies Man openly proclaimed that he would court any woman at all including skanks, providing the woman weighs no more than 250 pounds.  A night of romance would generally revolve around a bottle of Courvoisier.
After finally going too far during a broadcast, Leon is fired, but he receives a note from one of his former flames who wants him to come back to her—and is willing to support him in high style. This sounds just fine with Leon, except that the woman didn't sign her name, and now Leon has to backtrack through his numerous conquests of the past and figure out who wants him to work his love magic. Meanwhile, a secret group called the Victims of the Smiling Ass (V.S.A. for short), consisting of the angry husbands and boyfriends whose women have cheated with Leon, have discovered Leon as their target and are now hot on his trail, eager to get revenge.

Plot B: In 1920s America, Mary, a young girl exposed from her infancy to evil influences, is in love with Harry, a sculptor, but for the sake of financial gain becomes engaged to be married to the rich banker Jackson Harber, a much older man, and the former lover of her mother. Harry attempts suicide. By her abandoned behaviour, including her attempted seduction not only of Harber's adolescent son, Eduard, but also of Eduard's tutor, a priest, Mary drives Harber to the verge of suicide as well. The first historical sequence shows Mary as the Queen of Syria who cruelly executes a young goldsmith and jeweller (played by the same actor as Eduard). Back in the present, Mary has arranged an assignation with both Harber and Eduard, neither knowing of the intentions of the other, at night in a summerhouse. While waiting for them she falls asleep: an Expressionist dream shows Harber and Eduard fighting over her, and Eduard killing his father. This is succeeded by the main historical sequence, the wickedness and destruction of Sodom, in which Mary now appears as Lea (Lia), Lot's wife. The dreams shock Mary into a realisation of the true nature and consequences of her behaviour, and she returns in penitence to Harry.