The protagonist, seventh-grader Natalie Napoli, is given a yearlong assignment by her highly enthusiastic new science teacher, Mr. Neely. The students must each choose a question to which they are dying to know the answer. In their lab notebooks, they are supposed to record notes, hypotheses, and observations about their questions, in addition to completing other class assignments. However, Natalie also uses the notebook to record notes about everything that is going on in her life. This creates the novel’s structure.

During class, Natalie writes about her overeager teacher and about a fellow student who annoys her, Mikayla Menzer. She also mentions that her mother is “sick,” so her family needs to tighten up its spending. Mr. Neely asks Natalie to pay attention during class, but she continues writing.

A few days later, Mr. Neely has students read their questions aloud in class. Natalie hadn’t chosen one yet, so she makes fun of the teacher’s usage of hashtags instead. This makes her best friend, Twig, laugh. Meanwhile, other students have real questions. The most impressive ones come from Dari, an annoyingly smart boy.