Background <p>Neoadjuvant chemoimmunotherapy provides a good pathological response in patients with resectable head and neck squamous cell carcinoma (HNSCC). Currently, there is no comprehensive systematic review that rigorously evaluates and summarizes the existing studies. In this study, we aimed to synthesize the results on the efficacy of neoadjuvant chemoimmunotherapy in resectable HNSCC to obtain higher-level evidence.</p> Methods <p>The PubMed, Web of Science, Scopus, and Academic Search Complete&#xa0;(EBSCO) databases, along with ClinicalTrials.gov, Google Scholar, and conference abstracts, were comprehensively searched. The publication dates of the literature were limited to January 2015–July 2024. Meta-analysis was performed using a random-effects model. The percentage of major pathological response (MPR), pathological complete response (pCR), and overall disease-free survival (DFS) were synthesized. The odds ratios of a combined positive score (CPS) ≥ 20 for MPR and the diagnostic performance of using radiological objective response to determine MPR were further explored.</p> Results <p>A total of 13 studies with 458 patients who received neoadjuvant chemoimmunotherapy and 443 patients who underwent curative surgery were included. The pooled MPR, pCR, and overall DFS rates were 61%, 37%, and 91%, respectively. The odds ratios of a CPS ≥ 20 for achieving MPR was 2.09 compared with those with a CPS &lt; 20. The sensitivity of using radiological objective response to determine MPR was 0.91 and the specificity was 0.46, with an area under the curve of 0.76.</p> Conclusion <p>Neoadjuvant chemoimmunotherapy showed promising results for resectable HNSCC. A CPS ≥ 20 can be used to screen for treatment-sensitive patients, and radiological examinations can be used to detect pathological response. Definitive conclusions require data from longer follow-up periods and controlled studies.</p>