BACKGROUND: Advanced non-small cell lung cancer (NSCLC) remains a challenging condition with limited treatment options. Pembrolizumab, a programmed death-1 (PD-1) inhibitor, has emerged as a promising therapy, necessitating a comprehensive analysis of its efficacy and safety. METHODS: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a thorough search across major electronic databases to compile studies evaluating Pembrolizumab's efficacy and safety in treating advanced NSCLC. Thirteen studies were included based on stringent inclusion and exclusion criteria, focusing on the objective response rate (ORR), disease control rate (DCR), and adverse event incidence. Statistical analyses assessed study heterogeneity and effect sizes, employing fixed or random-effects models as appropriate. RESULTS: The meta-analysis revealed an ORR of 0.46 (95% CI: 0.44-0.49) and a DCR of 0.74 (95% CI: 0.69-0.79), indicating significant tumor control and disease management. Sensitivity analyses confirmed the robustness of these findings. The overall incidence of adverse events was reported as 36% (95% CI: 32% to 40%), reflecting a manageable safety profile. Publication bias evaluation showed no significant bias, affirming the reliability of the results. CONCLUSIONS: Pembrolizumab exhibits substantial efficacy in reducing tumor burden and controlling disease in patients with advanced NSCLC, alongside a consistent safety profile. These findings support its continued use and further research into optimizing treatment strategies.