<p>Chemotherapy and thoracic radiotherapy are essential for cancer control but commonly induce cardiac inflammation and progressive fibrosis that undermine long‑term survivorship. Chemo/radiation‑induced oxidative stress and cardiomyocyte death promote immune cell infiltration, establishing a self‑sustaining inflammatory milieu that activates fibroblasts and drives inflammatory responses. The resulting myocardial stiffening and contractile dysfunction contribute to symptomatic heart failure, arrhythmias, and reduced quality of life. Conventional cardioprotective agents offer partial benefit yet are limited by suboptimal delivery to injured myocardium. Natural products have shown interesting cardioprotective effects. However, low bioavailability of these agents can reduce their efficacy. Nanoparticles can improve the bioavailability and circulation time of these agents, thereby improving their cardioprotective effects. On the other hand, nanoparticle platforms enable targeted modulation of drug biodistribution, lowering cardiac exposure to cytotoxic agents. Preclinical and translational studies demonstrate improved left ventricular function, reduced histologic fibrosis, and maintained antitumor efficacy following treatment with nanoformulations of anticancer drugs or cardioprotective agents. These approaches promise improved myocardial protection without interfering with anticancer efficacy. In this review, we examine the molecular drivers of chemo/radiotherapy-induced cardiac inflammation and fibrosis and evaluate nanomedicine platforms designed to mitigate inflammatory and fibrotic responses.</p>