Although anthracyclines have markedly improved treatment outcomes for cancer patients, their use is associated with a wide variety of cardiovascular complications. These include, arrhythmias, ventricular enlargement, hypertension, dilated cardiomyopathy, and congestive heart failure. Such adverse conditions may be further exacerbated by inflammatory processes, specifically those initiated by mitochondrial dysfunction, which leads to cardiac cell death and ventricular dysfunction. Understanding the mechanisms that underlie the cardiotoxicity of anthracyclines is of paramount importance in reducing the cardiovascular morbidity associated with cancer therapy. In this article we provide an up to date overview of the role played by mitochondrial dysfunction in the pathogenesis of cancer therapies-induced cardiotoxicity. Given the significant clinical implications and wide usage of Doxorubicin therapy, this article primarily focuses on the influence of this chemotherapeutic agent and its cytotoxic effects on mitochondrial dysfunction and cardiac injury. The updated insights compiled in this article may support developing preventive approaches against cardiotoxicity by strategically targeting mitochondrial signaling pathways and inhibiting the inflammatory responses as potential therapeutic interventions. Ultimately, such initiatives may support and enhance patient outcomes while preserving the therapeutic efficacy of cancer treatments.