The film opens by following Art Critic Morf Vanderwalt (Jake Gyllenhaal) as he attends the opening of an exhibit in Miami Beach. Morf is a highly opinionated critic who wields a tremendous power: his reviews often break new artists. Also in attendance are gallery owners (Rhonda Haze played by Rene Russo), several artists (Piers played by John Malkovich), and other Avant-Garde patrons of the arts.
Josephina (played by Zawe Ashton) discovers the body of artist Vetril Dease who lived in her building. When looking into his upstairs studio Josephina finds a large number of intriguing paintings. Also found were ashes of other paintings - the artist was trying to destroy his own works - but why? Josephina overlooks the reason and takes the paintings to Rhoda.
Unknown to either of them, the dead artist lived a horrible life which resulted in commitment to an asylum. Then a series of deaths start, each related to the stolen paintings. In order to increase the value of each painting, Rhoda decides to manufacture scarcity by removing some of them. The person chosen to move some of the paintings meets a gory death. Then the art collector who aspires to get some of the paintings dies in a gruesome manner. Before long the snooty art critic realizes that it is the paintings. They truly are "Art to Die For'. But he is too late, the paintings take revenge on the art patrons whose sole interest in them is using them to make money. Both Morf and Rhoda succumb to the sinister canvases.
The closing credits are run over the video of an artist who escaped the revenge of the paintings. He ignored the monetary value and is merrily creating something original for himself.