Background <p>Asthma patients with comorbid chronic rhinosinusitis or nasal polyps (CRS/NP) often experience poor asthma control. However, the comparative efficacies of biological therapies in this subgroup remain unclear.</p> Methods <p>A comprehensive search of multiple databases was conducted to identify randomized controlled trials (RCTs) on biological therapies targeting uncontrolled asthma that included CRS/NP data. The outcomes of interest were annual asthma exacerbation rate (AER), pre-bronchodilator forced expiratory volume in one second (pre-BD FEV1), asthma control questionnaire (ACQ) scores, and sinonasal outcome test (SNOT-22) scores. Pairwise meta-analyses were performed based on the presence or absence of CRS/NPs. Subsequently, random-effects network meta-analyses were conducted to perform indirect comparisons of the individual biological therapies.</p> Results <p>Eleven eligible RCTs evaluating tezepelumab, dupilumab, mepolizumab, and benralizumab were identified. Omalizumab and reslizumab were excluded because subgroup data were not available. Pairwise meta-analyses demonstrated significantly greater improvement effects of biological therapies on all outcomes in patients with CRS/NP than in those without CRS/NP (<i>p</i> &lt; 0.01). In the network meta-analyses, for CRS/NP patients, tezepelumab showed the most pronounced reduction in AER (rate ratio 0.17; 95% confidence interval [CI] 0.09, 0.29), while benralizumab (mean difference [MD] 0.30 L; 95% CI 0.19, 0.40) exhibited the greatest improvement in pre-BD FEV1. Tezepelumab demonstrated the most substantial improvement in the ACQ scores (MD -0.80; 95% CI -1.25, -0.35), whereas mepolizumab (MD -11.80; 95% CI -19.75, -3.85) was associated with the greatest improvement in the SNOT-22 scores.</p> Conclusions <p>In the management of asthma with CRS/NP, it is crucial to select biological therapies that consider specific improvements in individual outcomes.</p>