<p>Heart failure (HF) treatment remains one of the major challenges in cardiovascular disease management, and its pathogenesis requires further exploration. Cardiac metabolic remodeling is of great significance as a key pathological process in the progression of HF. The complex alterations of metabolic substrates and associated enzymes in mitochondria create a vicious cycle in HF. These changes lead to increased reactive oxygen species, altered mitochondrial Ca²⁺ handling, and the accumulation of fatty acids, contributing to impaired mitochondrial function. In this context, mitophagy plays a significant role in clearing damaged mitochondria, thereby maintaining mitochondrial function and preserving cardiac function by modulating metabolic remodeling in HF. This article aims to explore the role of mitophagy in cardiac metabolic remodeling in HF, especially in obesity cardiomyopathy, diabetic cardiomyopathy, and excessive afterload-induced heart failure, thoroughly analyze its molecular mechanisms, and review the therapeutic strategies and prospects based on the regulation of mitophagy.</p> Graphical Abstract <p>Cardiac metabolic remodeling acts as a key pathological process in the progression of heart failure (HF), which leads to impaired mitochondrial function and deteriorate cardiac function. In this context, mitophagy plays a critical role in maintaining mitochondrial integrity and functionality by clearing damaged mitochondria under metabolic remodeling. In this case, mitophagy offers an important therapeutic strategy to mitigate the progression of HF and improve the outcome of HF. There are various molecules associated with mitophagy that constitute a complex cross – interacting network and play a role in the progression of HF, such as PINK1, Parkin, LC3, Atg5, Atg12, ULK1, and AKT. In addition, several promising treatments for regulating metabolism are evident in promoting mitophagy, including SGLT2i, GLP-1RA, β-OHB, metformin, and omentin-1. In a word, with ongoing research into mitophagy and the rapid advancement in biotechnology, targeted mitophagy therapy for HF is expected to become a clinical strategy targeting metabolic remodeling in the near future, offering new hope for HF.</p> <p></p>