As oncologic therapies continue to advance, the overall survival of cancer patients has markedly increased. Nevertheless, virtually every anticancer treatment modality is accompanied by some degree of cardiotoxicity. Epidemiological data indicate that approximately 30 % of cancer survivors ultimately die from cardiovascular disease. Among the cardiotoxic agents, the anthracycline doxorubicin (DOX) is the most widely used. It effectively suppresses a variety of malignant tumors——including breast cancer, lymphoma, and acute leukemia——but its cardiac toxicity limits further escalation of clinical dosing. Literature reports identify a cumulative dose of ≥250 mg/m2 as the threshold of high risk, with roughly 25 % of patients receiving DOX developing varying degrees of myocardial injury; severe cases progress to heart failure. Even at cumulative doses below the traditional safety limit, some patients exhibit cardiac dysfunction after the first administration, suggesting that cardiotoxicity is not solely a linear function of dose. DOX related cardiotoxicity can be classified as acute (hours to days after administration), sub acute (weeks to months), and chronic/late onset (years later). Most patients initially exhibit only mild reductions in left ventricular ejection fraction (LVEF) or subtle abnormalities in global longitudinal strain (GLS), often without symptoms. Recently, cardiac biomarkers (cTn, NT proBNP) combined with high sensitivity echocardiography (speckle tracking) have been recommended for monitoring high risk individuals, enabling detection of subclinical injury before overt LVEF decline. Currently, several preventive and therapeutic approaches are used in clinical practice, which can be summarized into the following four points. (1) Dose limitation and administration strategies: fractionated low dose regimens, liposomal encapsulation, or continuous infusion lower peak plasma concentrations, thereby reducing cardiac exposure. (2) Pharmacologic prophylaxis: β blockers (e.g., carvedilol) and ACE inhibitors/ARBs have shown protective effects on LVEF in some randomized trials, though results remain inconsistent and require larger confirmatory studies. (3) Metabolic targeted interventions: animal experiments indicate that activation of PPARα or supplementation with L carnitine restores fatty acid oxidation and improves ATP generation, suggesting metabolic modulators as promising cardioprotective candidates. (4) Lifestyle modifications: regular aerobic exercise up regulates mitochondrial biogenesis genes (PGC-1α) and reduces reactive oxygen species (ROS) production; small clinical studies have demonstrated a potential benefit in attenuating cTnT elevation. However, DOX-induced cardiotoxicity has not been effectively controlled, indicating that the core mechanism underlying DOX-related cardiac toxicity remains unidentified. Cardiomyocytes are high energy demand cells, and metabolic dysregulation is considered a central component of DOX induced cardiotoxicity. DOX disrupts myocardial metabolic balance through several interrelated pathways. (1) Oxidative stress and mitochondrial damage: DOX generates abundant ROS within cells, leading to mitochondrial membrane potential loss, lipid peroxidation, and iron accumulation, which suppress electron transport chain activity and markedly reduce ATP synthesis efficiency. (2) Autophagy dysregulation: DOX interferes with autophagic flux, preventing the clearance of damaged mitochondria and further aggravating apoptosis and inflammatory responses. (3) Inflammation and cytokine release: oxidative stress activates NF-κB, up-regulating pro inflammatory cytokines such as TNF-α and IL-6, creating a chronic inflammatory microenvironment that weakens myocardial contractility. (4) Epigenetic modifications: studies have shown that DOX alters DNA methylation and histone acetylation patterns in cardiomyocytes, affecting the expression of key metabolic genes (e.g., PGC-1α, CPT-1) and further inhibiting fatty acid β oxidation. These mechanisms collectively lead to suppressed fatty acid oxidation and compensatory up regulation of glycolysis, manifested by an elevated lactate/pyruvate ratio, accumulation of medium chain acyl carnitines, and a pronounced decline in ATP production. The resulting energy deficit precipitates left ventricular contractile dysfunction and, ultimately, heart failure. Despite extensive basic and clinical research on DOX cardiotoxicity, a unified risk assessment model and precise interventions targeting metabolic disturbances remain lacking. This review systematically summarizes recent progress on DOX induced cardiotoxicity and highlights that impairment of myocardial energy metabolism is a central mechanism of injury, thereby deepened our understanding of how impaired myocardial energy metabolism drives DOX induced injury, we can move toward safer chemotherapy protocols that achieve “cure cancer without harming the heart”.