The story takes place after the events of Second Contact, which involved the TNG crew being transported to the Marvel Universe, where they aid the X-Men against Kang the Conqueror. However, a mysterious force (later revealed, to the reader, to be the entity Q) causes the X-Men to be dragged into the Star Trek universe (depicted both in the novel and on the final page of Second Contact); though this happens to the X-Men immediately (from their point of view) after parting with the crew of the U.S.S. Enterprise-E, a noticeable period of time has passed for the crew since returning to their own timeline.
The X-Men and Enterprise crew face a problem all too familiar to the Marvel mutants: a planet where some of the population have been spontaneously developing destructive, and often uncontrollable, super-powers, causing them to be quarantined and shunned by their fellow citizens—until, that is, one of the "Transformed" with the power to cause earthquakes escapes and leads his fellow super-powered outcasts in a revolution. Matters worsen when it is discovered that these beings had been genetically engineered by an aggressive alien race as living weapons, and now their creators were coming to collect them by force. When the Enterprise is dispatched by the Federation to assist in investigating the Transformed crisis, they are attacked by a ship belonging to this other race, its weapons proving powerful enough to deplete the Enterprise's shields in just two hits.
Working with the X-Men, the Enterprise crew manage to disable the ship, Nightcrawler teleporting himself and Data over to the enemy ship through its shields- Data being selected due to his knowledge of alien technology and his inability to get tired ensuring that he would not be negatively affected by Nightcrawler's abilities- and allowing them to shut down the ship's defenses long enough for a team including Worf, Banshee and Archangel to transport over and do further damage. With the ship disabled, the X-Men join the away teams down on the planet, with Storm soon defeating the rogue leader of the Transformed, even as Data and Nightcrawler manage to convince the other Transformed to listen to them by demonstrating how they also differ from those around them but are still willing to trust others. The enemy ship is later disabled when an away team- including Counselor Troi, Wolverine and Colossus- manage to transport over to the ship, Wolverine interrogating the ship's captain to learn that they created the Transformed via a unique gene therapy and were intending to 'harvest' them for use in later missions of conquest.
The crisis resolved, Dr. Crusher- aided by a hologram of Professor X created based on information acquired from the mansion's computers during the Enterprise's visit to the X-Men's universe- manages to develop a cure for the Transformed before the X-Men are sent back to their reality. It is revealed at the end that this situation had been at least partly caused by Q and Uatu the Watcher, Q having manipulated events to send the X-Men through to the 'Trekverse' to help the Enterprise deal with the Transformed crisis.