The novel began as Clarke's, but when ill health and a psychological (or possibly neurological) form of writer's block prevented him from making progress, he handed over his notes and the incomplete manuscript to Pohl, who, in close consultation with Clarke, completed the novel. Clarke reviewed the final manuscript in early March 2008, just days before he died.

The book is about a young Sri Lankan mathematician who finds a short proof of Fermat's Last Theorem, while an alien invasion of Earth is in progress.

The Last Theorem is set in Sri Lanka in the early- to mid-21st century and follows the life of a mathematician, Ranjit Subramanian. While studying at Colombo University, he becomes obsessed with Fermat's Last Theorem, a conjecture made by Pierre de Fermat in 1637, for which he claimed to have conceived a proof that he never wrote down.The proof eluded mathematicians across the world for over 350 years, until in 1995 British mathematician Andrew Wiles published a 100-page proof of the theorem. But not everyone was "satisfied" with Wiles's proof because it used twentieth century mathematical techniques not available in Fermat's time.