Background: It is well known that chronic inflammation can enable immune escape by suppressing immune surveillance. This promotes cancer growth and development, which forms the basis of immune checkpoint inhibitors use. Pan-Immune-Inflammation Value (PIV), a type of immune-inflammatory biomarker, has shown predictive value in various cancer patient populations (colorectal, melanoma, breast, oesophagus, ALK-positive lung cancer) and patients with ANCA-associated vasculitis. We aimed to evaluate the role of PIV as a predictive biomarker in advanced non-small cell lung cancer (NSCLC), whereby immune checkpoint inhibitor therapy is frequently used. Methods: We conducted a retrospective review of advanced NSCLC patients who received immunotherapy in the National University Hospital, Singapore between January 2015 and January 2022. PIV was calculated as: (neutrophil count × platelet count × monocyte count)/lymphocyte count, with the median value used to distinguish between high and low PIV. Kaplan–Meier method and Cox proportional hazards regression models were used for survival analyses. Results: 203 patients were included in the study. The median age was 63, 70% were males, 76% were Chinese, 83% had ECOG Performance Status ≤1 and 70% had adenocarcinoma histology. The immunotherapy agents used were Pembrolizumab (82%), Nivolumab (13%) and Atezolizumab (5%). Chemotherapy was given in conjunction with immunotherapy in 37% of the population. The median PIV value derived was 790 and patients with a low baseline PIV experienced better progression-free survival (PFS) and overall survival (OS). The median PFS was 249 days in PIV-low vs 145 days in PIV-high cohorts (hazard ratio for progression or death from any cause [HR] 0.58, 95% Confidence Interval [CI] 0.40-0.86, p < 0.01) and the median OS was 794 days in PIV-low vs 420 days in PIV-high cohorts (HR 0.69, 95% CI 0.49-0.96, p = 0.03). Patients who had higher PIV, ECOG performance status ≥2, liver metastases, immunotherapy exposure in 2^nd line or later, use of immunotherapy alone without chemotherapy had worse OS in univariate analysis, but only PIV (HR = 1.61, 95% CI 1.08-2.40, p < 0.02) was an independent prognostic factor in multivariate analysis. Amongst the patients with known PD-L1 status (n = 158), univariate analysis showed that PD-L1 ≥1 and PD-L1 ≥50 were not prognostic for OS whereas PIV remained an independent prognostic factor in both univariate and multivariate analyses. Conclusions: PIV appears to be a strong predictor of survival outcomes for patients with advanced NSCLC receiving immunotherapy as part of their cancer treatment. Prospective clinical trials are required to validate the predictive value of PIV in NSCLC patients receiving immunotherapy, as well as evaluating PIV’s performance against PD-L1.