<p>Introduction. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy improves survival in selected patients with peritoneal metastases, but postoperative morbidity remains substantial. The relationship between disease burden and perioperative outcomes in routine practice requires further clarification. This study evaluated postoperative morbidity and the predictive value of tumor burden together with immunonutritional and inflammatory indices. Methods. This case series analysis included 53 consecutive patients treated between October 2020 and October 2025 at a single institution. The primary endpoint was any postoperative complication within 30 days. Secondary endpoints included severe complications (Clavien–Dindo grade III or higher), reoperation, 30-day mortality, operative duration, and hospital stay. The Peritoneal Cancer Index, Prognostic Nutritional Index, and Systemic Immune-Inflammation Index were assessed using receiver operating characteristic analysis and logistic regression. Results. Postoperative complications occurred in 45.3% of patients; severe morbidity developed in 15.1%, and 30-day mortality was 3.8%. Higher Peritoneal Cancer Index values were strongly associated with postoperative complications and showed good ability to identify patients at increased risk. Lower Prognostic Nutritional Index values independently predicted morbidity. Combining tumor burden with immunonutritional status further improved risk stratification. Conclusion. Postoperative morbidity after cytoreductive surgery is strongly influenced by tumor burden, while immunonutritional reserve provides additional prognostic information. Integrating tumor burden with host-related biological status may enhance perioperative risk stratification and support individualized surgical planning.</p>