"Tonari no 801-chan R" is a short-form anime series that humorously explores the dynamics of a romantic relationship between a human man and a female yaoi fangirl who is also a Fujoshi. The protagonist, a young man referred to as "R-kun," lives a relatively ordinary life until he discovers that his girlfriend, 801-chan, is deeply immersed in the world of yaoi, a genre of fictional media focusing on romantic relationships between male characters. The series delves into the comedic and often exaggerated situations that arise from 801-chan's obsession with yaoi, as she frequently imagines R-kun and other men in romantic scenarios, much to his bewilderment and occasional discomfort.

The narrative is episodic, with each short episode presenting a new scenario where 801-chan's fantasies clash with R-kun's reality. These situations often highlight the cultural phenomenon of fujoshi culture in Japan, where women enjoy creating and consuming male-male romantic content. The series uses humor to explore the misunderstandings and challenges that arise from 801-chan's passion, as R-kun struggles to reconcile his girlfriend's interests with his own sense of normalcy. Despite the comedic tone, the series occasionally touches on themes of acceptance and understanding in relationships, as R-kun gradually learns to navigate 801-chan's world without losing his own identity.

The characters are central to the series' appeal. R-kun is portrayed as a somewhat reserved and grounded individual, serving as the straight man to 801-chan's eccentricities. 801-chan, on the other hand, is vibrant and unapologetically passionate about yaoi, often blurring the lines between fantasy and reality. Supporting characters, such as friends and acquaintances, occasionally appear to add depth to the interactions and provide additional comedic moments. The series maintains a lighthearted tone throughout, with its humor deriving from the contrast between R-kun's mundane perspective and 801-chan's imaginative, yaoi-fueled worldview.