Background Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, yet treatment responses remain heterogeneous. With the widespread implementation of coronavirus disease 2019 (COVID-19) vaccination, uncertainty persists regarding its impact on antitumor efficacy in patients receiving ICIs. While vaccine safety has been extensively studied, the association between COVID-19 vaccination and ICI therapeutic outcomes has not been systematically evaluated. Methods We conducted a systematic review and meta-analysis of observational studies examining the association between COVID-19 vaccination and oncologic outcomes in patients treated with ICIs. PubMed, Embase, and Scopus were searched from 2020 to December 31, 2025. Primary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes included objective response rate (ORR) and disease control rate (DCR). Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using random-effects models. Results Ten observational studies comprising 4,929 patients receiving ICIs were included. COVID-19 vaccination was associated with significantly improved PFS (pooled HR = 0.66, 95% CI 0.48–0.90) and OS (pooled HR = 0.51, 95% CI 0.39–0.66) compared with no vaccination. Vaccinated patients showed numerically higher ORR (pooled OR = 1.74, 95% CI 0.89–3.41) and DCR (pooled OR = 1.74, 95% CI 0.83–3.46), although these differences were not statistically significant. Subgroup analyses by vaccine platform and cancer type yielded consistent associations. Conclusions COVID-19 vaccination is associated with improved survival outcomes in patients receiving ICIs. Although the observational nature of available data warrants cautious interpretation, the consistency of findings and their biological plausibility support the clinical compatibility of vaccination with ICI therapy, but causal or synergistic effects cannot be established from these data. These results reinforce current vaccination recommendations and highlight the need for prospective studies to further elucidate underlying mechanisms and optimize integration with cancer immunotherapy. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420261277938.
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