Background: Radical Cystectomy (RC) is the gold-standard treatment for recurrent high grade T1 or muscle-invasive bladder cancer. Nutritional status is a well-defined independent predictor of overall survival post-RC. Various prognostic biomarkers have been proposed as surrogates for nutritional status to help predict postoperative outcomes. These biomarkers include albumin, anemia, thrombocytopenia and sarcopenia. Recently, the Hemoglobin, Albumin, Lymphocyte, Platelet (HALP) score has been postulated as an all-encompassing biomarker and has been shown to predict overall survival (OS) post-RC in a single previous study. Due to the paucity of studies looking at HALP and RC outcomes, and optimal cutoffs for HALP have not been defined. Our study sought to analyze and optimize HALP thresholds for OS, as well as examine the Psoas Muscle Index (PMI) as a possible additional predictor that can be used with HALP. Methods: Seventy-three RC patients were evaluated from 2010 to 2021. Of 73 RC patients, 50 had sufficient pre-operative laboratory data to calculate HALP. Sixty-two patients had CT scans to analyze PMI, which was calculated using patient height and the psoas major muscle cross-sectional area measured at the L3 vertebral level. Patient date of surgery, tumor grade and stage, American Society of Anesthesiologists (ASA) Classification, survival status, and date of last contact were extracted from our institutional cancer registry. X-tile software was used to find optimal biomarker cutoffs for HALP. The Cox Proportional Hazards model was used to identify predictors of OS. Results: Median age was 67 (58-74) years, 58 (79.5%) were male, and 36 (49.3%) received neoadjuvant/adjuvant chemotherapy. Forty-seven (64.4%) had pathological stage ≥pT2, 25 (35.7%) had lymph-node involvement, and 4 (5.5%) had palliative surgery. Median HALP score was 28 (21 – 42). Median PMI was 569 (456 –700). Fifty-six (76.7%) had an ASA ≥ 3. Median follow up was 29.3 months (12.0– 51.9). Forty-eight (65.8%) were alive at last follow-up. HALP (continuous variable) was a significant predictor of OS on multivariable Cox regression analysis (HR 0.95, 95% CI 0.90 - 0.99) (P = 0.021), adjusting for age, sex, and node involvement; PMI and ASA were not significant. X-tile analysis showed an optimal HALP cutoff of 25.0. Patients with HALP < 25 had inferior OS (median, 32.5 months) compared with those with HALP ≥ 25 (median, not reached) (P = 0.025). Conclusions: We conclude that patients with low HALP Score were shown to have a significantly inferior OS, with an optimum HALP cutoff of 25.0. We further suggest that the HALP score can be a reliable prognostic biomarker to assist in nutritional management before surgery. PMI was not a significant predictor of OS and did not add value to HALP score. Future studies may investigate better measures of sarcopenia, which could potentially be combined with HALP score to better predict OS in RC patients.