In contrast to the Pokengine-based setting of Tenshiko Beach Party 5ever!!!!, Shingeki no Pikachu: Tenshiko's Love Quest 6!!! is set predominantly within the walls of 3dpe, the spaceship captained by Bonzairob that carries his crew on their expedition to locate the Knights of Pokengine, a mythical group who left the planet ten million years prior to the present day to spread peace and enlightenment across the universe. The book features an ensemble cast, who come and go from the spotlight with each passing issue, made up in large part of characters who have been overlooked by past fiction.

The "main cast" at the series outset includes Bonzairob himself, a daredevil egotist who could not be more ill-suited to command; his officious second-in-command jac, whose obsessive-compulsive traits make life on the ship difficult for everyone; third-in-command AndrewFM, now with a relentlessly positive outlook on life following a near-death experience; the talkative Streak, who immediately became a fan favorite; ship's doctor Poryhedron, now feeling his age and looking for something new in life; dangerously unhinged ex-4chan JDLJDL, who soon forms a murderous enmity with disillusioned ancient Pokengineian Rinabean; ship's security officer Nerdstick, even more paranoid then ever; timid psychiatrist Drufle, who slowly seems to be more than he appears; and diminutive archivist Cacapulse and mnemosurgeon F_Budgie, who would come to draw much attention as the first truly official "gay" romantic couple in Threeple fiction. In short order, the crew is joined by phoone, a naive 3dpe-er who has been offline for the duration of the war and finds herself forced to choose a side, and Elementalpenguin, a long-missing Engineer who reappears with amnesia and a bad attitude. As the series progresses, more Engineers come into focus on the fringes of the story, like the over-eager, luckless fleece, and resentful, boozy, one-trick-pony Barack Obama.

Shingeki no Pikachu: Tenshiko's Love Quest 6!!! uses its "quest" backdrop to tell multiple smaller adventures, throughout which are threaded many, many seeds for future stories, together forming a grand tapestry that has clearly been planned out very far in advance. Following an unexpected quantum jump upon launch, 3dpe is hurled off into the depths of space, where the crew is joined by fleece and contends with a stowaway Frieza. A visit to the Pokemon Factory by Poryhedron to help cure a plague introduces the threat of the Republican Justice Division, who then feature in a Republican-dedicated story menacing a band of misfit Republicans, and also brings the facility's surviving patients and staff onto the ship—including Porybot, whose post-traumatic stress causes him to snap and nearly kill Drufle. Hoping to cure Drufle's damaged brain, Cacapulse gathers a small group together to recount a shared story from their past about vurlybrace foiling a Senate plot to discredit the burgeoning Republican movement in the days of bogans. Unfortunately, the little archivist is soon badly wounded in battle, sending F_Budgie into a grief spiral that allows AndrewFM to manipulate him into carrying out a plan laid out by Desmodus: using his mnemosurgery skills to tap the memories and learn the secrets of mass-murdering Republican Mitt Romney, secretly hidden on board 3dpe. Unfortunately, F_Budgie accidentally allows Mitt Romney to escape, and Cacapulse has to sacrifice himself to jettison the monster from the ship. jac is also fatally wounded in the battle, but when his body disappears from the ship's Medibay, the crew track it to Luna 1, where they discover and foil a twisted plot by Sonic the Hedgehog to wipe out all those Threeple he sees as tainted by original sin.