Sorafenib, a multi-targeted tyrosine kinase inhibitor, is used to treat various cancers, including hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). While effective, it can cause significant cardiovascular toxicity, including hypertension, thrombosis, cardiac ischemia, and left ventricular dysfunction. This review explores the mechanisms behind sorafenib-induced cardiovascular toxicity, such as endothelial dysfunction, mitochondrial dysfunction, endoplasmic reticulum stress, dysregulated autophagy, and ferroptosis. It also discusses potential treatment strategies, including antioxidants and renin-angiotensin system inhibitors, and highlights the association between sorafenib-induced hypertension and treatment efficacy in cancer patients. Emerging research suggests a link between sorafenib-induced glycolysis, drug resistance, and cardiovascular toxicity, necessitating further investigation. Understanding these mechanisms is crucial for optimizing sorafenib therapy and minimizing cardiovascular risks in cancer patients. Sorafenib inhibits the vascular endothelial growth factor receptor (VEGFR) and RAF, leading to cardiovascular toxicity by disrupting vascular homeostasis. The drug's complex pharmacological profile contributes to adverse effects and drug resistance. Sorafenib-induced hypertension is a common side effect, with a significant association with treatment efficacy. Management strategies include antihypertensive medications, close monitoring, and dose adjustments. Other cardiovascular effects include myocardial ischemia, decreased left ventricular ejection fraction, congestive heart failure, and coronary artery spasm. Mechanisms of toxicity involve endothelial damage, NO inhibition, endothelin-1 system activation, mitochondrial dysfunction, endoplasmic reticulum stress, autophagy dysregulation, and ferroptosis. Treatment options include antioxidants, renin-angiotensin system inhibitors, and metabolic reprogramming agents. The review also highlights the potential link between drug resistance and cardiovascular toxicity, emphasizing the need for further research to elucidate shared mechanisms and develop effective therapeutic strategies.Sorafenib, a multi-targeted tyrosine kinase inhibitor, is used to treat various cancers, including hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). While effective, it can cause significant cardiovascular toxicity, including hypertension, thrombosis, cardiac ischemia, and left ventricular dysfunction. This review explores the mechanisms behind sorafenib-induced cardiovascular toxicity, such as endothelial dysfunction, mitochondrial dysfunction, endoplasmic reticulum stress, dysregulated autophagy, and ferroptosis. It also discusses potential treatment strategies, including antioxidants and renin-angiotensin system inhibitors, and highlights the association between sorafenib-induced hypertension and treatment efficacy in cancer patients. Emerging research suggests a link between sorafenib-induced glycolysis, drug resistance, and cardiovascular toxicity, necessitating further investigation. Understanding these mechanisms is crucial for optimizing sorafenib therapy and minimizing cardiovascular risks in cancer patients. Sorafenib inhibits the vascular endothelial growth factor receptor (VEGFR) and RAF, leading to cardiovascular toxicity by disrupting vascular homeostasis. The drug's complex pharmacological profile contributes to adverse effects and drug resistance. Sorafenib-induced hypertension is a common side effect, with a significant association with treatment efficacy. Management strategies include antihypertensive medications, close monitoring, and dose adjustments. Other cardiovascular effects include myocardial ischemia, decreased left ventricular ejection fraction, congestive heart failure, and coronary artery spasm. Mechanisms of toxicity involve endothelial damage, NO inhibition, endothelin-1 system activation, mitochondrial dysfunction, endoplasmic reticulum stress, autophagy dysregulation, and ferroptosis. Treatment options include antioxidants, renin-angiotensin system inhibitors, and metabolic reprogramming agents. The review also highlights the potential link between drug resistance and cardiovascular toxicity, emphasizing the need for further research to elucidate shared mechanisms and develop effective therapeutic strategies.