One prominent theme in Breakfast of Champions is the rightful role of the artist, a particularly complex issue in a society that excels at transforming art into a commodity and is heavily invested in the comforting illusions offered by Washington, Wall Street, and Hollywood. Through his creation of a self-aware, anti-novel, Vonnegut seeks to dissuade readers from striving to "live like people invented in story books." This theme revisits a favorite concept of Vonnegut's, explicitly articulated in the preface to the 1966 reissue of Mother Night: "We are what we pretend to be, so we must be careful about what we pretend to be."

In Breakfast of Champions, the wealthy Dwayne Hoover is juxtaposed with the visionary Kilgore Trout. Central to their conflict is the theme of free will. Toward the novel's conclusion, Hoover reads Trout's book, Now It Can Be Told, which claims he is the sole entity in the universe possessing free will, while everyone else is simply a robot. This revelation appears to confirm Hoover's sense of isolation and sparks a violent psychotic break, resulting in both protagonists being left damaged, both physically and spiritually.

Nevertheless, Breakfast of Champions provides a ray of hope for positive change. While empirical data implies that life operates like a machine, intuition—articulated by minimalist artist Rabo Karbekian—suggests the presence of an "unwavering and pure" "immaterial core" within people, the "I am to which all messages are sent." In this context, Breakfast of Champions symbolizes Vonnegut's attempt to define a new form of humanism, envisioning a world where "we are healthy only to the extent that our ideas are humane."

The novel consistently highlights the challenges of authentic communication, showcasing superficial dialogues and unsuccessful efforts to express truth. In one absurd instance, Vonnegut details the physical dimensions of all the main characters, yet the language spoken in Midland City is an equally meaningless blend of clichés and routine responses. Before descending into madness, Dwayne Hoover begins to repeat the last words spoken to him, but the people of Midland City fail to notice this change. The book demonstrates that ineffective communication can be dangerous. After Hoover's violent outburst, "it shook up Trout to realize that even he could bring evil into the world — in the form of bad ideas." Despite this, when Trout encounters "What is the purpose of life?" scrawled on a men's room wall, he promptly replies, "To be the eyes and ears and conscience of the Creator of the Universe, you fool."