"Danna ga Nani wo Itteiru ka Wakaranai Ken" centers on the daily life of a married couple, Hajime Tsunashi and Kaoru Tsunashi, whose relationship is defined by their contrasting personalities and interests. Hajime is a passionate otaku with a deep love for anime, manga, and gaming, often immersing himself in his hobbies to the point of obliviousness. Kaoru, on the other hand, is a pragmatic and hardworking office worker who struggles to understand her husband's otaku tendencies. Despite their differences, the couple shares a genuine affection for one another, and their interactions highlight the humorous and endearing aspects of their relationship.

The series unfolds through a series of short, episodic vignettes that depict the couple's everyday experiences. Hajime's otaku habits frequently lead to comedic misunderstandings, as Kaoru attempts to navigate his eccentricities while maintaining her own sense of normalcy. Whether it's Hajime's obsession with collecting figurines, his tendency to quote anime lines in inappropriate situations, or his elaborate cosplay endeavors, Kaoru often finds herself exasperated yet amused by his antics. Over time, she begins to develop a deeper appreciation for his passions, even if she doesn't fully share them.

Supporting characters, such as Hajime's equally otaku-minded friends and Kaoru's colleagues, add further layers to the narrative. These characters often serve as foils or catalysts for the couple's interactions, providing additional comedic and situational dynamics. The series balances humor with moments of genuine warmth, showcasing the couple's ability to navigate their differences and grow closer despite their contrasting worlds.

The episodic structure of the series allows for a lighthearted exploration of themes such as communication, compromise, and the blending of different lifestyles within a marriage. While the humor often stems from Hajime's otaku quirks, the underlying message emphasizes mutual understanding and the importance of embracing each other's individuality. The series avoids heavy drama, instead opting for a slice-of-life approach that highlights the charm of everyday moments shared between two people who, despite their differences, genuinely care for one another.