The story follows three drifters in present-day Seattle who are tormented by strange dreams of the Kalpa, a city one hundred trillion years in the future.

In an attempt to fend off the approaching Typhon, leaders of the dying Earth sent for Polybiblios, a human living with the Shen, an ancient alien race.

After the Shen system fell, and the Chaos surrounded Earth, its leaders instructed everybody to convert themselves from primordial (real) matter to noötic (virtual) mass.

The novel alternates between the Kalpa and present-day Seattle, where three drifters, Ginny, Jack and Daniel are in possession of sum-runners, small stone-like talismans that give them "fate-shifting"[4] abilities, whereby they can jump between fate-lines (world lines in a multiverse).

The breeds, programmed to see Ishanaxade as their "mother", are also drawn to Nataraja, and Jebrassy and Taidba find their counterparts Jack and Ginny in the ruined city.

The Kalpa falls to the Chaos, but in Nataraja, the sum-runners and their Babel fragments are united and history is recreated, causing the Typhon, now a failed god, to implode.

[10] Bear's early influences included science fiction authors Robert A. Heinlein, Isaac Asimov and Poul Anderson.

[13] In an interview with Andromeda Spaceways Inflight Magazine in September 2008, Bear said that what inspired him to write City at the End of Time was the question, "What if we're still primitive in our thinking [about physics and cosmology]?

"[1] Bear told Locus magazine in August 2008 that he had found what appears to be a "continuity" in British science fiction: H. G. Wells's The Time Machine (1895), Arthur C. Clarke's The City and the Stars (1956), and Hodgson's The House on the Borderland (1908) and The Night Land (1912), all speculate on the evolution of humankind in the deep future.

"[14] He said that Bear pays homage to William Hope Hodgson's 1912 novel, The Night Land, with which City at the End of Time shares a number of plot elements.

Books feature prominently in the novel in both present-day Seattle and the Kalpa in the future, and Heck sees it as "a metaphor that anyone whose life is built around books—whether as a writer, reader, or bookseller—can readily empathize with.

In the Kalpa, Polybiblios creates Babel fragments ("Borgesian libraries that do not end") that, when brought together, will form a "backstory" that retells the history of the universe and overwhelms the Typhon.

SFF World said the novel is similar to Stephen King's Dark Tower, where "an ultimate destination that defies both space and time are at the heart" of both stories.

[19] SFF World described City at the End of Time as "an Epic Science Fiction novel [with] elements of thriller and horror with some downright creepy characters.

[21][22] A review in Publishers Weekly described City at the End of Time as a "complex, difficult and beautifully written tale [that] will appeal to sophisticated readers who prefer thorny conundrums to fast-paced action".

[23] A reviewer for the Library Journal said the novel "plung[es] readers into a visceral experience of cosmological theory and the big creation stories of mythology".

[16] Speculative fiction writer Simon Petrie writing in Andromeda Spaceways Inflight Magazine was impressed by the book's "grandiosity to the total synthesis of cosmology and myth", and Bear's "ability to encapsulate a universal future history in just the one book",[25] but found the mix of science, fantasy, horror, mythology and religion a little "incongruous" at times.

[25] In a review in the online speculative fiction magazine Strange Horizons, Tony Keen was critical of Bear's novel, saying that the present and future passages "do not mesh terribly well", and that it is "too long" with "too many ideas".

He described the "end of time" sequence as "the most powerful science fictional moment in this entire book", saying that he found it "far more scary, far more gripping, than any supernatural intervention".

Johnson wrote that while Bear's depictions of events on a grand scale, like the decay of Seattle, are good, his portrayal of the key players against this backdrop is not as strong.