Background: Meta-analyses show that increasing body mass index (BMI) may be associated with improved overall survival (OS) and progression free survival (PFS) compared to those with lower BMIs in patients receiving immunotherapy (IO). Pretreatment elevated platelet lymphocyte ratio (PLR) has been attributed to inferior PFS and OS in patients receiving IO. Our study evaluated real world data of Stage IV Non-Small Cell Lung Cancer (NSCLC) patients receiving first line (1L) treatment regimens involving immunotherapy while evaluating prognostic utility of BMI and PLR. Methods: Of the patients treated at USC Norris Comprehensive Cancer Center and LAC+USC Medical Center from 2015-2022, we looked at 75 Stage IV patients without EGFR, ALK, ROS1 mutations who received 1L IO therapy. Primary outcomes included PFS and OS from time of IO with a particular interest for patients with pre-treatment BMI < 22 and PLR > 180. Patients with previous IO exposure were excluded. Kaplan-Meier analysis using log-rank test was performed to evaluate for OS. Multivariate Cox proportion hazards regression was used for multivariate analysis of OS. Results: The median age at start of IO was 67.5 years with 49 (65.3%) males. 24 (32.0%) had BMI < 22. 40/70 (57.7%) had PLR > 180 at the start of 1L IO. Adenocarcinoma was the most common histology 50 (66.7%). 22 (29.3%) had PD-L1 > TPS 50% and 20 (26.7%) had PD-L1 TPS 1-49%. Pembrolizumab was the most common IO used 60/75 (80%) and 43/75 (57.3%) received chemotherapy with IO. Patients with a BMI < 22 had an inferior OS (BMI < 22: 13.1 vs. BMI > 28: 37.4 months (mos), p-value = 0.0420) with a trend towards worse PFS (BMI < 22: 6.2 mos vs. BMI > 28: 16 mos, p = 0.1702). Patients with PLR > 180 had an inferior PFS (4.4 vs. 11.1 mos, p-value = 0.025) and OS (8.3 vs. 23.0 mos, p-value = 0.0277). A composite of BMI < 22 and PLR > 180 had the worst OS (p-value = 0.0385) with a trend towards worse PFS (p-value = 0.1702). (Table 1) Multivariate analysis for OS controlling for age, smoking, gender, PD-L1 TPS, and histology showed that BMI (HR: 0.8739, 95% CI: 0.7966-0.9492) and PLR > 180 (HR: 2.286, 95% CI: 1.102-4.916) were significant for higher mortality risk. Conclusions: Patients with a composite profile of BMI < 22 and PLR > 180 had a significantly worse OS. This highlights the importance for pre-treatment screening for low BMI and high PLR to help provide additional supportive care in these patients prior to IO therapy.