Ten years after the events of xxxHOLiC Shunmuki, a melancholic Kimihiro Watanuki has taken over the shop formerly run by the mysterious Yuuko due to a promise he made to her. His companions Maru, Moro, and Mokona live together with him in relative contentment, and some familiar faces arrive every now and then: former rival turned-steadfast friend Shizuka Doumeki, and the former psychic prodigy Kohane Tsuyuri. While Kohane studies folklore under Doumeki at university, they encounter a case that is perfect for the master of the shop. Eventually, Watanuki receives a visit from Doumeki's grandfather, Haruka. He requests that Watanuki investigates his grandson's dreams. While inside the dream world, he discovers how their past adventures played out from Doumeki's perspective of view, leading Watanuki to discover truths from 10 years ago and secrets about the ties that bind their friendship.

After the murder of their parents, 11-year-old twin brothers Thor and Rai Klein are sent away from their home planet. They find themselves awakening on the terraformed planet of Chimaera, where carnivorous plants dominate and the few humans who live there are divided into four groups known as Rings. Soon after, they meet a young man by the name of Zagi, and the twins learn that only the Jyu Oh Sei—the one who conquers these four Rings—is allowed to leave the planet. Driven by the desire to return home and discover the truth behind the death of his parents, Thor resolves to survive in the harsh, merciless environment of Chimaera. However, he quickly learns there is more than meets the eye in this strange ecosystem. As Thor is swept up in the politics that entangle the Rings, he uncovers more about his parents' murder, and ultimately, humanity's fate as a whole.

The Labyrinth is an expansive space deep underground where humans live in clusters known as colonies. Over the years, the surface has become a distant memory—even perhaps only a fantasy to those who have never experienced its wonders. Making sure humanity survives the harsh conditions of the underground, a colony's citizens can take on a variety of specialized jobs. These include Workers, who mine precious ore to fuel the colonies, and Markers, who journey into the Labyrinth's surprisingly lush environment to bring back information that eases navigation. However, humanity also faces a threat to its existence—creatures called kaijuu whose sizes range from that of a small child to an enormous building, and are hostile to any human they see. Moreover, kaijuu that are large enough can force their way into the colonies, further increasing their threat level. Memenpu is a nine-year-old college graduate whose inventions have greatly benefitted the Workers in her local colony. Recently, however, she has been dreaming of a place with a neverending ceiling not bound by bedrock. These aspirations fuel her desire to become a Marker and explore the Labyrinth's vast unknown in search of such a fantastical place. Despite her father Gagumber's vehement disagreement, a certain incident with the kaijuu jumpstarts a dangerous yet exciting adventure that will surely alter humanity's course forever.

After Brook questions the origin of the Mini Merry name, Usopp and Chopper Tony Tony recall the adventures of the Straw Hat Crew's beloved ship, friend, and crew member—the Going Merry. Ussop abandons the crew for a fight over the Going Merry while Robin Nico leaves with the government's top assassin group, CP9. In order to bring the crew back together, Monkey D. Luffy and the remaining Straw Hats follow Robin to rescue her from the claws of the World Government.