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Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) treats peritoneal carcinomatosis by circulating heated (42 °C) chemotherapeutic solutions intra-abdominally, but risks severe systemic hyperthermia due to inconsistent temperature control protocols. Conventional methods like cooled fluids, ice packs, and cooling devices often prove inadequate, with slow response times and limited precision during open surgery. This case underscores the need for vigilance regarding perioperative hyperthermia during HIPEC and suggests employing targeted temperature management (TTM) with a 33 °C target, which limited core temperature rise from 36.1 °C to 37.4 °C (Δ1.3 °C) over 90 minutes of HIPEC-lower than fluctuations in non-TTM cases. TTM's real-time feedback enables rapid, automated shifts from warming (CRS phase) to cooling (HIPEC phase), reducing reliance on multiple adjuncts and minimizing thermal deviations. This approach enhances patient safety, optimizes therapeutic delivery, and may improve outcomes in CRS-HIPEC.