As Sandworms of Dune begins, the passengers of the no-ship Ithaca continue their nearly two-decade search for a new home world for the Bene Gesserit, while Duncan Idaho evades the tachyon net of the old couple Daniel and Marty, now known to be thinking machine leaders Omnius and Erasmus.

Back in the Old Empire, Mother Commander Murbella of the New Sisterhood attempts to rally humankind for a last stand against the thinking machines.

The new Face Dancers continue to infiltrate the main organizations of the Old Empire at all levels, having also sent their gholas of Paul Atreides (called Paolo) and the Baron Vladimir Harkonnen to the thinking machine capital, Synchrony.

Navigator Edrik and his faction have commissioned Waff, the imperfectly awakened ghola rescued by the Guild from the Bene Gesserit attack on Bandalong, to create "advanced" sandworms able to produce the melange they so desperately require.

He accomplishes this by altering the DNA of the sandtrout stage and creating an aquatic form of the worms, which are then released into the oceans of Buzzell.

Adapting to their new environment, these "seaworms" quickly flourish, eventually producing a highly concentrated form of spice, dubbed "ultraspice".

Meanwhile, Murbella commissions Ix to copy the destructive Honored Matre Obliterators for use on the fleet of warships she has ordered from the Guild.

The thinking machine plague arrives at Chapterhouse and cripples the Sisterhood, but they rally the unified humankind into one last great stand.

Scytale, the last Tleilaxu Master, finally reawakens his own ghola's past memories, but only by dying in front of his younger self.

Waff realizes that the pearl of Leto II's awareness that each sandworm carries had foreseen the Honored Matre attack on Rakis and caused them to have buried themselves deep beneath the planet's surface.

Knowing the planet has begun healing itself, Waff is consumed by a worm, rejoicing that his prophet has finally returned.

The saboteurs are eventually revealed to be the Rabbi and the ghola of Thufir Hawat, who had apparently been murdered and replaced with Face Dancers back on the planet of the Handlers during the events of Hunters of Dune.

Victorious, Paolo consumes the ultraspice; overwhelmed by the rapid onset of perfect prescient vision, he slips into a coma.

Paul, at the urging and efforts of Yueh, Chani, and Jessica, slowly regains his past memories and is able to repair the damage to his body using Bene Gesserit physiological control.

As this is happening, Murbella has all the new ships in place and is finally ready to launch her fleet against Omnius's oncoming armada.

Sheeana and the young Leto II ghola free the sandworms from the Ithaca's cargo hold, and the worms wreak havoc throughout Synchrony.

Amused by Khrone's attempt to seize power, Erasmus explains that a fail-safe system had been built into the Face Dancers.

On Qelso, the gholas of Stilgar and Liet-Kynes continue to aid in the attempt to hold back the expanding desert, while simultaneously teaching the planet's occupants how to adapt to the changes that will inevitably come.

Looking forward to the time when his memories will be restored, Lady Jessica finds solace in the fact that she will be reunited with her Duke.

The novel was commercially successful, and praised by Jackie Cassada of the Library Journal: Complex in structure though never hard to follow, this sequel to Hunters of Dune ties together the threads left by Chapterhouse: Dune, bringing closure to a saga of planetary birth and death and human courage and hubris.

[4]Conversely, the novel was criticized by Publishers Weekly for its writing and storytelling methods: Longtime collaborators Herbert and Anderson set themselves a steep challenge—and, in the end, fail to meet it—in this much anticipated wrapup of the original Dune cycle (after 2006's Hunters of Dune) [...] Though pacing is brisk and the infrequent action scenes crackle with tension, only two minor characters—gholas, who are young clones with restored memories, of Suk doctor Wellington Yueh and God-Emperor Leto II—acquire real depth.

Everyone else is too busy reacting to mostly irrelevant subplots like sabotage aboard the no-ship Ithaca, a plague devastating the planet of Chapterhouse and the genetic engineering of marine-dwelling sandworms.

The lengthy climax relies on at least four consecutive deus ex machina bailouts... Series fans will argue the novel's merits for years; others will be underwhelmed.

Anderson said that Frank Herbert's notes included a description of the story and a great deal of character background information.