While Moon Tiger provides rich characterizations, settings, and social themes, its primary concern is with epistemology. In this novel Lively takes to a radical extreme the ideas about history, time, and reality that she more tentatively addressed in her six earlier novels.

At the novel's outset, seventy-six-year-old Claudia, who is lying in a hospital bed dying of cancer, makes the startling announcement, "I am writing a history of the world." Although we at first assume, as does the patronizing nurse who is attending her at the time, that this is just the deluded rambling of senility, by the end of the novel we realize that Claudia has in fact given us a history of the world of sorts. That is, the mixture of personal memories, flashbacks, and ruminations about historical events that constitutes both Claudia's consciousness and the book itself effects the kind of historical account that this unconventional historian believes is the most authentic. Her method is a massive demonstration of her Berkeleyan-like theory that history is a function of consciousness, that in a sense history exists only insofar as a mind is thinking about it. Claudia unapologetically points out that what she is giving us is "the history of the world according to Claudia" and declares, "Egocentric Claudia is once again subordinating history to her own puny existence. Well — don't we all?"

In mixing reflections on historical events with recollections of events in her own life, Claudia suggests that history is filtered through the personal lens of the individual mind contemplating it. Further, her method suggests that linear time is an illusion — or rather a constructed, not an absolute or natural, feature of reality — for "inside the head, everything happens at once." Although historical events, as well as personal events, have actual temporal occurrences, their more significant reality resides in the mind of the person reflecting on them, and, as the structure of Claudia's mind — and hence of Moon Tiger, which is essentially a portrait of her mind — demonstrates, these reflections occur in a recursive, associationist, nonlinear fashion.

Contributing to this theme about the subjective nature of reality is the book's narrative structure. Using her kaleidoscopic method (see separate entry on The Road to Lichfield) much more freely here than in her earlier novels/ Lively recounts several of the book's episodes from different points of view, suggesting how each individual's mindset shades the episode differently.

Yet another epistemological concern addressed in Moon Tiger is the relationship between language and reality. Underlying this novel is the postmodernist notion that language constructs reality. Lively has characters frequently give voice to both this idea (for example, Claudia states, "I control the world as long as I can name it" and "Language tethers us to the world; without it we spin like atoms") and to the post-structuralist idea that "reality" is merely a text (Claudia's brother Gordon refers to life as a "narrative," Tom Southern refers to his and Claudia's lives as "stories," and Claudia disparagingly compares "reality" to other fictions: "Moments shower away; the days of our lives vanish utterly, more insubstantial than if they had been invented. Fiction can seem more enduring than reality").