<p>Ferritinophagy is a crucial intracellular process mediated by the selective autophagy receptor nuclear receptor coactivator 4 (NCOA4), which plays a central role in maintaining iron homeostasis by regulating ferritin degradation. In recent years, its function as a key interface between autophagy and iron metabolism has attracted considerable attention owing to its pathophysiological relevance in cardiovascular diseases (CVDs). This review systematically delineates the molecular mechanisms of ferritinophagy, including the formation of the NCOA4–ferritin complex, lysosomal degradation pathways, and the multilayered regulatory networks involved. Particular focus is given to the dual role of ferritinophagy in cardiovascular pathology, encompassing myocardial ischemia–reperfusion injury (MIRI), atherosclerosis (AS), and diabetic cardiomyopathy (DCM). While moderate ferritinophagy activity is essential for maintaining adequate cardiac iron supply, its excessive activation leads to labile iron accumulation, oxidative stress via the Fenton reaction, and ferroptosis, thereby exacerbating myocardial injury and pathological remodeling. Consequently, this article provides a comprehensive overview of pharmacological strategies targeting ferritinophagy, including direct inhibition approaches (e.g., NCOA4 small interfering RNA (siRNA) and lysosomal inhibitors) and indirect modulation strategies (e.g., ferroptosis inhibitors and natural compounds). Finally, challenges to clinical translation are addressed, particularly regarding tissue specificity, drug delivery efficiency, and long-term safety. Future research directions are proposed, including the development of organ-specific targeting strategies and the exploration of combination therapies, with the aim of offering novel insights and potential therapeutic avenues for the prevention and treatment of CVDs.</p>