The story is narrated by an unnamed female protagonist who believes she is the last person on Earth. She wanders through various landscapes, seemingly deserted cities, and landscapes, reflecting on her memories, thoughts, and philosophical musings. As she navigates her solitary existence, she recalls snippets of her past life, relationships, and encounters with various historical figures.

Throughout the novel, the protagonist grapples with questions of existence, reality, language, and identity. Her reflections often draw on the philosophical ideas of Ludwig Wittgenstein, whose work serves as a recurring motif in the narrative. The protagonist's musings touch on themes such as the limitations of language, the nature of perception, the search for meaning, and the human condition in the face of isolation and uncertainty.

As the narrative unfolds, the reader is presented with fragmented glimpses of the protagonist's past life, including her relationships with family members, lovers, and friends. These memories are interspersed with philosophical anecdotes, literary references, and historical trivia, creating a collage-like structure that challenges traditional notions of storytelling.

Overall, "Wittgenstein's Mistress" is a thought-provoking exploration of existential themes, presented through a fragmented narrative that blurs the boundaries between fiction, philosophy, and autobiography. The novel's experimental style and philosophical depth have earned it acclaim as a seminal work of postmodern literature.