"Hōkago NyanNyan" centers around a group of high school girls who form a club dedicated to caring for stray cats in their neighborhood. The protagonist, Yui, is a shy and reserved student who discovers a litter of abandoned kittens on her way home from school. Her initial hesitation to get involved is overcome when she meets Rina, an outgoing and confident classmate who shares her love for animals. Together, they decide to create the "NyanNyan Club," a space where they can provide shelter, food, and medical care for the stray cats they encounter.

As the club grows, they are joined by other students, each with their own motivations and personalities. Miko, a studious and pragmatic girl, initially joins to fulfill a school requirement but gradually becomes emotionally invested in the cats. Meanwhile, Aya, a mischievous and energetic underclassman, brings a playful dynamic to the group, often lightening the mood during challenging moments. The girls face various obstacles, including limited resources, school regulations, and the emotional toll of seeing some cats suffer or disappear. Their efforts to balance their responsibilities as students with their commitment to the cats form the core of the narrative.

The series explores themes of compassion, responsibility, and community as the girls work together to make a difference in the lives of the strays. Their interactions with the cats and each other reveal personal growth and deepening friendships. Subplots include Yui overcoming her shyness to advocate for the club, Rina confronting her fear of abandonment stemming from her own childhood, and Miko learning to balance her academic ambitions with her newfound empathy. The story also touches on the broader issue of animal welfare, as the girls collaborate with local veterinarians and animal shelters to address the challenges faced by stray animals in their community.

Throughout the series, the NyanNyan Club’s activities evolve from informal caregiving to organized initiatives, such as fundraising events and adoption drives. The girls’ dedication inspires their peers and teachers, fostering a sense of collective responsibility. The narrative concludes with the club achieving a significant milestone, securing a permanent space for their activities and ensuring the well-being of the cats they have come to love. The series ends on a hopeful note, emphasizing the impact of small, determined efforts in creating meaningful change.