Dandy is a groovy, pompadour-wearing man who explores the stars in search of strange aliens for money, desiring to visit his favorite place: BooBies, the best diner in all the cosmos. Traversing the galaxies in his trusty ship, the Aloha Oe, Dandy is accompanied by his two equally unique friends: QT, the vacuum cleaner robot; and Meow, an alien with a cat-like appearance. Although exciting, Dandy's job is never simple, and each new day promises a completely different, thrilling adventure. Together, Dandy and his crew get dragged into perilous journeys, misadventures in romance, and out of this world scenarios—all whilst steering clear of the evil scientist, Dr. Gel of the Gogol Empire.

Kou Ichinomiya is the son of a wealthy businessman who holds a firm belief in his elite status. As such, he is determined to avoid becoming indebted to anyone; but one day, after a run-in with some mischievous kids on Arakawa Bridge, he ends up falling into the river running underneath. Luckily for him, a passerby is there to save him—but now, he owes his life to this stranger! Angered by this, Kou insists on paying her back, but this may just be the worst deal the arrogant businessman has ever made. The stranger—a stoic, tracksuit-wearing homeless girl known only as Nino—lives in a cardboard box under the bridge and wants only one thing: to fall in love. Asking Kou to be her boyfriend, he has no choice but to accept, forcing him to move out of his comfortable home and start a new life under the bridge!

Mahiro Yasaka is just an ordinary high school student, until one day he is suddenly attacked by a dangerous monster. Just when everything seems to be lost, he is saved by a silver-haired girl named Nyaruko, who claims to be the shape-shifting deity Nyarlathotep from horror author H. P. Lovecraft's Cthulhu Mythos, sent by the Space Defense Agency to Earth. She explains to Mahiro that the creature chasing him was an alien called Nightgaunt, who had planned on abducting and selling him as a slave. After rescuing him from the alien, the Lovecraftian deity falls madly in love with Mahiro and forces herself into his household, much to his chagrin. Moreover, they are soon joined by two others from the fictional universe: Cthuko, a girl obsessed with Nyaruko, and Hasuta, a young boy easily mistaken for a beautiful female. Together, the three eccentric aliens protect Mahiro from the various extraterrestrial dangers that threaten both his and Earth's well-being, all the while making his life a living hell.

The exciting antics of Wagnaria return as more ridiculous incidents occur, friendships are deepened, and new feelings are discovered. In addition to Souta Takanashi and his wacky co-workers, more eccentric personalities join the family restaurant: Haruna, Hyougo Otoo's missing wife, who has a habit of getting hopelessly lost through the sewer system; Kirio Yamada, Aoi's older brother, who is able to withstand Mahiru Inami's deadly punches; and twins Youhei and Mitsuki Mashiba, Kyouko Shirafuji's juniors who do not get along. Absurdity, romance, and hilarity are all on the menu for the Wagnaria family restaurant!