Itsuki Nakano is the fifth and youngest daughter of the Nakano quintuplets, a fact that belies her often serious and responsible demeanor. She is distinguishable by her long, wavy red hair, which she typically wears down, and a pair of star-shaped hairpins on either side of her head, along with a distinctive hair antenna (ahoge) at her crown. Her character color is red, and she is the only one of the five sisters with naturally wavy hair. In her school uniform, she wears the outfit most properly, with a red vest and the longest skirt among her siblings, and she often dons a pair of red-rimmed square glasses when studying due to her poor eyesight.

Raised in a household that experienced poverty before their mother remarried, Itsuki was deeply influenced by her late mother, Rena. Following her mother's passing during her elementary school years, Itsuki made a personal vow to adopt a maternal role within the family, striving to maintain order and set a proper example for her sisters. This sense of responsibility is a core part of her identity, driving her motivation to become a teacher, as she wishes to honor her mother's legacy and experience the same feeling of gratitude and fulfillment that comes from educating others.

Personality-wise, Itsuki is known for being earnest, diligent, and well-mannered. She consistently speaks in a formal and polite tone (keigo), which contributes to her strait-laced image. While she often acts mature and attempts to be the voice of reason, she is still very much a high school girl with her own set of vulnerabilities. She has a stubborn streak and can hold a grudge, as demonstrated by her initial rejection of Fuutarou Uesugi's tutoring after a quarrel where he made a rude comment about her eating habits and criticized her hairpins. Despite her best efforts, she is not a naturally gifted student; she lacks efficiency in test-taking, often spending too much time on single problems, though she excels in science. Her most prominent and endearing trait is her enormous appetite, which is a running source of humor, as she is constantly seen eating or thinking about food. This love for eating has led to her having a secret side gig as a renowned food critic who posts reviews under the pseudonym "M.A.Y.".

Itsuki's role in the story begins as the first quintuplet to meet Fuutarou, which establishes a unique but initially contentious bond between them. She is one of the most resistant to his tutoring at the start, but as the narrative progresses, she becomes one of his most trusted confidantes. Their relationship develops into a close, platonic friendship characterized by mutual respect, open communication, and occasional bickering. She is particularly close to her sister Nino, as they share similar interests like yoga and morning sit-ups, poor eyesight, and a guarded personality, and Nino is often very protective of her. Itsuki also forms a strong bond with Fuutarou's younger sister, Raiha, who sees her as an older sister figure.

Throughout the series, Itsuki's character development is subtle but significant. She gradually overcomes her stubbornness and learns to be more honest with herself and others. A key part of her arc involves her knowledge of the past between Fuutarou and her sister Yotsuba. At Yotsuba's request, Itsuki disguises herself as a girl from Fuutarou's past named "Rena" to test his feelings and encourage him, demonstrating her willingness to put her sister's happiness before her own. She is notably the last of the quintuplets to recognize the romantic feelings developing among her sisters for Fuutarou, as she is described as being quite dense about matters of love. This naivety extends to her own heart, as she does not fully acknowledge any potential romantic feelings she may have harbored until after Fuutarou has made his final choice. Ultimately, her journey focuses on personal growth and self-sufficiency, leading her to successfully achieve her dream of becoming a dedicated teacher.

In terms of abilities, while she struggles with overall academic efficiency, Itsuki is a hardworking and perceptive individual with a strong sense of detail. Her strongest academic subject is science. Her observation and deduction skills are sharp enough to maintain her secret identity as the food critic M.A.Y., a persona with enough influence to significantly boost a restaurant's business. She also works as an assistant at a cram school, an experience that furthers her journey toward becoming an educator. Aside from her intellectual pursuits, Itsuki maintains a disciplined morning routine of sit-ups and yoga, which she does in an attempt to manage her weight despite her large appetite.