Renal cell carcinoma (RCC) is distinguished by its varied metabolic reprogramming driven by tumor suppressor gene dysregulation and oncogene activation. Tumors can adapt nutrient uptake and metabolism pathways to meet the altered biosynthetic, bioenergetic and redox demands of cancer cells, whereas conventional chemotherapeutics and molecular inhibitors predominantly target individual metabolic pathways without addressing this adaptability. Flavonoids, which are well-known for their antioxidant and anti-inflammatory properties, offer a unique approach by influencing multiple metabolic targets. The present comprehensive review reveals the intricate processes of RCC metabolic reprogramming, encompassing glycolysis, mitochondrial oxidative phosphorylation and fatty acid biosynthesis. The insights derived from the present review may contribute to the understanding of the specific anticancer mechanisms of flavonoids, potentially paving the way for the development of natural antitumor drugs focused on the metabolic reprogramming of RCC. Contents 1. Introduction 2. Anticancer drugs targeting metabolic reprogramming 3. Role of flavonoids in RCC metabolic reprogramming 4. Toxicity associated with flavonoids 5. Dietary bioactive compounds as chemopreventive agents 6. Combination therapy with bioactive compounds against cancer 7. Summary 8. Conclusion