Background <p>Although immune checkpoint inhibitors have transformed the treatment landscape in advanced non-small cell lung cancer (NSCLC), reliable and accessible biomarkers to predict survival and treatment response remain limited. This study aimed to evaluate the prognostic and predictive utility of the Magnesium–Immune Prognostic Score (MIPS), a composite index based on neutrophil-to-lymphocyte ratio and serum levels of C-reactive protein, magnesium, albumin, calcium, phosphorus, lactate dehydrogenase, and uric acid, in metastatic NSCLC patients receiving second-line nivolumab.</p> Methods <p>This retrospective study included 95 patients with advanced NSCLC treated with nivolumab. The MIPS was constructed by integrating three predefined component indices: the Inflammation-Mediated Immunity Index (IMI), the Mineral and Nutritional Index (MINI), and the Aggressive Tumor Index (ATI). Survival outcomes were analyzed using ROC curves, Kaplan–Meier methods, and Cox regression models.</p> Results <p>Among 95 patients, those with high MIPS had significantly shorter progression-free survival and overall survival than those with low MIPS (<i>p</i> &lt; 0.001). In multivariable Cox analysis, high MIPS remained an independent predictor of poor OS (HR: 2.694, <i>p</i> &lt; 0.001). Among all indices, MIPS showed the strongest discriminative ability (AUC = 0.696). All four composite indices—IMI, MINI, ATI, and MIPS—were significantly associated with treatment response, with high-score groups demonstrating higher rates of good response (CR + PR), and MIPS showing the strongest association (<i>p</i> &lt; 0.001).</p> Conclusion <p>The MIPS represents a simple, accessible, and clinically applicable prognostic and predictive tool for stratifying metastatic NSCLC patients receiving nivolumab. By integrating inflammatory, nutritional, and metabolic components, the score offers a holistic assessment of patient biology. Prospective validation studies are warranted.</p>