Heart failure (HF) is a complex and multifactorial disease that affects millions of people worldwide. It is characterized by metabolic disturbances of substrates such as glucose, fatty acids (FAs), ketone bodies, and amino acids, which lead to changes in cardiac energy metabolism pathways. These metabolic alterations can directly or indirectly promote myocardial remodeling, thereby accelerating the progression of HF, resulting in a vicious cycle of worsening symptoms, and contributing to the increased hospitalization and mortality among patients with HF. In this review, we summarized the latest researches on energy metabolic profiling in HF and provided the related translational therapeutic strategies for this devastating disease. By taking a holistic approach to understanding energy metabolism changes in HF, we hope to provide comprehensive insights into the pathophysiology of this challenging condition and identify novel precise targets for the development of more effective treatments.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.