According to data from the American Cancer Society, cancer is one of the deadliest health problems globally. Annually, renal cell carcinoma (RCC) and liver cancer cause more than 100,000 and 800,000 deaths worldwide, respectively [1–4], creating an urgent need to develop effective therapeutic treatments to increase patient survival outcomes. New therapeutic treatments are expected to address a major factor contributing to cancer’s resistance to standard therapies: oncogenic heterogeneity. Because gene expression can vary tremendously among different types of cancers, different patients of the same tumor type, and even within individual tumors, various metabolic phenotypes can emerge, making single-therapy approaches insufficient. This heterogeneity translates into changes in the landscape of metabolic enzymes and biomolecules within both the cancer cell and tumor microenvironment. Novel strategies targeting the diverse metabolism of cancers aim to overcome this obstacle, and though some have yielded positive results, it remains a challenge to uncover all of the distinct metabolic profiles of RCC and liver cancer. Nonetheless, the metabolic-oriented research focusing on these cancers has offered different, fresh new perspectives, which are expected to contribute heavily to the development of new therapeutic treatments.