The novel, which Bellow initially intended to be a short story, is a roman à clef about Bellow's friendship with the poet Delmore Schwartz. It explores the changing relationship of art and power in a materialist America. This theme is addressed through the contrasting careers of two writers, Von Humboldt Fleisher (to some degree a version of Schwartz) and his protégé Charlie Citrine (to some degree a version of Bellow himself). Fleisher yearns to lift American society up through art but dies a failure. In contrast, Charlie Citrine makes quite a lot of money through his writing, especially from a Broadway play and a movie about a character named Von Trenck - a character modeled after Humboldt.
Another notable character in the book is Rinaldo Cantabile, a wannabe Chicago gangster, who tries to bully Citrine into being friends and whose career advice to Citrine, focused solely on commercial interests, is the opposite of the advice Citrine was once given by his old mentor, Humboldt Fleisher, who valued artistic integrity above all other concerns.
Some critics, including Malcolm Bradbury, see the novel as a commentary on the increasing commodification of culture in mid-century America. Throughout much of the book, Bellow also analyzes, through the voice of Citrine, his thoughts about spirituality, poetry, and success in America.