In the near future, space aliens settle on earth and get along well with humans. Mayuko tries to concentrate on summer school classes while the alien NieA pesters her for lunch.
Mayuko is living in a bath house and going to cram school until she can afford to pay her way to college. NieA is an alien living in her closet who likes to build UFO's in her room. Many years ago, an alien ship landed and it's inhabitants integrated into Japanese society. Mayuko has little money and almost no food while NieA is a freeloader. At school Mayuko meets an old classmate named Chiaki who wants to come to her house and see the UFO. Embarrassed about her bad living state and roommate, she is reluctant. Her feelings are confirmed when NieA launches her UFO right through the roof.
Needing to do something to help the bath house get back in the black, Mayuko, Nenji and NieA go to the crater in search of an oil that rumor has it exists there. Along the way, the group are attacked by giant plants and they lose their Bento lunches. When they return, they use the oil for the furnace and mix in some dead plants to cause a nice aroma. All is well until the plants start growing.
Mayuko is greeted by a large Indian man who seems to be a pervert. NieA recognizes him as the owner of a convenience store as an alien. He invites Mayuko there for their opening and then invites NieA to the alien meeting. NieA ends up going to the meeting with the promise of free Bento. The meeting ends up being between about five aliens with Chada being the most outspoken one of the group. Of course, this leads her and NieA to blows and the meeting comes to an end.
Mayuko has started a new job at a European restaurant where she delivers food (although she tells Chiaki that she's a waitress). After NieA has stuck Chada with a food bill at the restaurant she works at, Chada pays a visit to the restaurant. Mayuko runs a delivery when Genzo shows up looking for her so that he can give her some rice. When NieA come in, she and Chada start to fight again. What else can go wrong for Mayuko?
Still in the red, the Enohana Bath house must do something to bring in customers. When NieA waltzes in with several parts from a video game store that has closed down, Kotomi (the owner and manager of the bath house) has an idea on how to get more customers. They advertise a game day with the customers playing against the employees - the winner gets a year of free baths.
When a new bath house opens in the crater, Kotomi asks NieA and Mayuko to investigate. Since they can't go inside or they'll be recognized, they enlist Genzo and Chiaki to help get intel from the inside. Outside the new bath house, Mayuko finds some interesting leaves that they are using in the bath house. Suddenly the back door opens and out walks Kaana, the Indian alien, and confronts them as the owner of the new bath house. Mayuko runs off with NieA in tow. Later at the Enohana Bath House, Genzo and Chiaki come back and are acting very strange. The group discover that the strange leaves Mayuko found are an illegal substance and the cops come to shut down the new bath house.
Chiaki asks Mayuko to go to a Go-Con with her. A Go-Con is a blind date with several guys and several girls in hopes that some of them can pair off. Chiaki reluctantly agrees. Meanwhile, NieA is building a new UFO on the roof when she picks up a signal through her radio. This had happened once before but now is much stronger and appears to be coming from the mother ship. After worrying about what to wear and her hair that need cutting, Mayuko calls Chiaki and tells her that she can't go to the Go-Con after all.
Mayuko is feeling down about how she yelled at NieA and skipped out on the the Go-Con. Later at cram school, she runs in to the group of girls that went to the Go-Con and they let her know that everything is okay with them about her cancelling. Meanwhile NieA goes to another alien meeting and has another fight with Karna. Mayuko, feeling better about things spends the rest of her money on a meal for her and NieA. Not everything goes as planned, however, when NieA comes home full from the alien meeting.
Mayuko is still upset with NieA's behavior while NieA decides that Mayuko's mood is caused by malnutrition. She heads to the junk yard to sell scap in order to buy her more nutritional food. When the junk man refuses her prices he suggests that she try a restricted area. When NieA goes there she receives a very strong signal from the mothership. Genzo shows up with more rice and he and Mayuko start talking about their childhood times together. Genzo asks if Mayuko still writes the stories that she used to tell him when he was depressed. Later NieA shows up with a nutritional meal for Mayuko - but she's been duped into buying a model instead.
When the restaurant that Mayuko works at gets a large party reservation, Mayuko goes to the supermarket for ingredients. Chie goes with her which turns out to be fortunate since Mayuko has never been inside a supermarket before. After the party leaves the restaurant, Chie sees fireflies for the first time and her father tells he about how Enohana used to be known for them - so to speak. NieA still tries to figure out what the mothership means by the "sayonara" signal she picked up.
NieA has been missing for some time now and Mayuko is starting to get worried. Meanwhile life goes on as the owner of the Enohana Bath House is pondering selling out. She tells Mayuko not to worry though since nothing has been decided yet. Mayuko starts to feel nostalgic towards the bath house and her home.
Kotomi has hired someone to fix the hole in the bath house roof. On her way to school Mayuko goes to the Alien Registration Office to see if there is any sign of NieA. They tell here that they have no information on anyone lower than an Under 5 classification. Later that day Mayuko gets a package from her mother. She says she cannot find any of the old notebooks that she used to write stories in but she did find some old pictures. The pictures show Mayuko and her family when they used to own and run the bath house. These cause Mayuko to get sad. Later, NieA has shown up out of the blue as if nothing has happened. When a storm blows through, Mayuko and NieA try to hold down the tarp over the semi-repaired roof. When they look up, they watch the mother-ship disappear in a sparkle of light.
Things continue pretty much as normal after the disappearance of the mothership. Chiaki and Mayuko talk about things now that it's gone and how NieA is doing. Later, Kotomi tells them that the bath house actually turned a profit. Genzo shows up with a large load of rice for Mayuko as Chiaki is leaving. Suddenly, NieA appears in a new UFO she'd been working on in secret. When the power on this runs out in mid-flight, she lands on the roof of the bath house and blows another hole in it.