<p>Heart failure (HF) is a heterogeneous clinical syndrome characterized by phenotype-specific metabolic remodeling (e.g., ischemic vs. nonischemic, HF with HFrEF vs. HFpEF), with impaired metabolic flexibility serving as a central pathophysiological link. The physiological basis of normal cardiac metabolic flexibility is outlined, and the temporal trajectories and molecular mechanisms of metabolic remodeling across compensated, early decompensated, and end-stage HF are delineated. Key mechanisms, including dysregulated mitochondrial quality control, imbalanced substrate utilization, and transcriptional dysregulation are examined. Furthermore, multidimensional metabolic therapeutic strategies are summarized, and the translational potential of novel biomarkers (e.g., ketone bodies, acylcarnitines) is discussed. It is indicated the efficacy of metabolic therapies depends critically on HF phenotype, disease stage, and global metabolic network integrity. Future research is prioritized metabolomics-based precise phenotyping, dynamic monitoring of remodeling trajectories, and the development of systematic regulatory strategies featuring multi-target combinations and cardiac-specific delivery, so as to advance the clinical translation of metabolic therapies for HF.</p>