Background <p>The second most common malignancy after breast cancer is lung cancer (LC). Small cell lung cancer accounts for 15%, while non-small lung cancer (NSCLC) accounts for 85% of cases. Immunotherapy has improved treatment outcomes in NSCLC. However, the role of systemic inflammation-based prognostic scores in predicting response to treatment is not clear. The meta-analyses aims to evaluate the prognostic/ predictive value of inflammatory biomarkers, including NLR, ALI, PLR, CRP, and mGPS, and their potential associated with overall survival in NSCLC patients receiving immunotherapy as first-line or second-line treatment.</p> Methods <p>A systematic review and meta-analysis was conducted following the Cochrane Handbook and PRISMA guidelines. Searches were performed in PubMed, Cochrane Library, and Web of Science for studies published until January 1, 2022, using specific keywords related to NSCLC, immunotherapy, inflammatory biomarkers and survival. Meta-analysis was performed using RevMan software, analyzing the hazard ratio (HRs) with a 95% confidence interval (CIs) primarily in relation to overall survival.</p> Results <p>Six thirty three records were identified, and 17 articles were included in the meta-analysis. The pooled analysis of NLR, ALI, PLR, CRP, and mGPS was significantly associated with OS without significant heterogeneity (NLR: HR = 2.15; 95% CI 1.60 – 2.87; <i>P</i>-Value &lt; 0.00001); (ALI: HR = 2.03; 95% CI 1.43 – 2.88; <i>P</i>-Value &lt; 0.0001); (PLR: HR = 4.06; 95% CI 2.14 – 7.67; <i>P</i>-Value &lt; 0.0001); (CRP: HR = 5.37; 95% CI 3.90 – 7.39; <i>P</i>-Value &lt; 0.00001); and (mGPS: HR = 3.27; 95% CI 1.26 – 8.28; <i>P</i>-Value = 0.01), respectively.</p> Conclusions <p>Systemic inflammatory biomarkers demonstrate independent prognostic/ predictive value in patients with advanced non-small cell lung cancer who receive immunotherapy as either the first-line or second-line therapy.</p>