(1) Background: Takotsubo cardiomyopathy, or stress cardiomyopathy, is an acute heart failure condition with transient left ventricular (LV) motion abnormalities but no significant coronary artery obstruction. It mimics acute coronary syndrome (ACS), with symptoms like chest pain, dyspnea, and ECG changes. (2) Case Report: We present the case of a 44-year-old female with relapsed colon cancer and peritoneal carcinomatosis. After undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), she experienced cardiac arrest from ventricular fibrillation 18 h postoperatively. Echocardiography revealed a reduced LV ejection fraction (20%) and apical akinesia, suggesting a Takotsubo Cardiomyopathy. Intensive resuscitation and inotropic support led to gradual recovery. Coronary angiography confirmed no coronary artery obstruction. (3) Discussion: This case highlights TTS as a rare but severe complication following major oncological surgeries, possibly triggered by both physical and emotional stressors. TTS should be considered in the differential diagnosis of perioperative cardiac events in cancer patients. (4) Conclusions: Prompt recognition and management of TTS in the perioperative period are crucial to improving outcomes, especially in high-risk oncological patients undergoing extensive surgeries.