Abstract: Metabolic remodeling, a hallmark of cancer, has gained increasing attention in the field. Targeting cancer metabolism is considered to open up a window for the discovery of targeted anticancer therapies. In the past decade, tremendous advancements have been made in the basic research on cancer metabolism, particularly in understanding the roles of altered metabolism and the underlying mechanisms in cancer malignancy. In contrast, the progress in the development of new therapeutics seems very slow, with only a few drugs approved for clinical use, indicating that there remains a huge gap between basic research and translational medicine. This review summarizes the challenges encountered in the development of metabolism-targeted therapies and proposes future directions from the perspective of drug discovery and translational medicine, aiming to provide insights for the development of therapies targeting cancer metabolism.