The spread of tumor within the peritoneal cavity is termed peritoneal carcinomatosis (PC). The most common etiologies are gastric, colorectal, ovarian, and appendiceal cancers. Despite the development of medical oncologic treatments for this disease group, poor responses to systemic therapies are often observed. Among the reasons for these are challenges in peritoneal vascularization and the mesothelial-mesenchymal transition of peritoneal fibroblasts. Unfortunately, systemic treatments have not been successful in alleviating PC. Complications such as intra-abdominal acid, cachexia, sarcopenia, bowel, and ureteral obstructions make management more complex in these patients treated due to PC. In patients with PC, interdisciplinary approaches supported by combined medical oncology– and modern technology–based devices, such as concomitant cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC), offer hope to these patients. Successful outcomes have been achieved in colorectal, ovarian, and appendiceal cancer cases with concomitant systemic chemotherapy and CRS + HIPEC–supported surgeries. However, the main problem still lies in the treatment of metastatic gastric cancer. The aim of this chapter is to present innovative and modern medical oncologic and surgical approaches in this challenging and complex disease through an interdisciplinary approach.