Chronic rhinosinusitis (CRS) with nasal polyps occurs in 6-57% of individuals with cystic fibrosis (CF). According to the EPOS 2020 guidelines, CF-related CRS is classified as secondary diffuse, non-type-2 CRS. In contrast, most nasal polyposis in the general population is associated with primary, type-2 CRS. This educationally-oriented classification system facilitates the categorization of CRS in distinct groups. However, it may suggest that each type of CRS is caused by a single underlying mechanism, potentially leading clinicians to overlook that, in reality, multiple factors can drive CRS development. The incidence of CRS stemming from multiple etiologies remains currently underexplored. We report an illustrative case of a CF patient with concomitant NSAID-Exacerbated Respiratory Disease (NERD), necessitating two distinct targeted therapies to achieve effective symptomatic relief.