Clear cell renal cell carcinoma (ccRCC) is a metabolic disease, of which the incidence rate is increasing worldwide. Renal carcinoma is characterized by mutations in target genes involved in metabolic pathways. Metabolic reprogramming covers different processes such as aerobic glycolysis, fatty acid metabolism, and the utilization of tryptophan, glutamine, and arginine. In the era of the multi-omics approach (with integrated transcriptomics, proteomics, and metabolomics), discovering biomarkers for early diagnosis is gaining renewed importance. Areas covered: In this review, we discuss the pathophysiological mechanisms underlying ccRCC metabolic reprogramming. In addition, we describe the emerging metabolomics-based biomarkers differentially expressed in ccRCC and the rationale for the recently developed drugs specifically targeting the ccRCC metabolome. Expert opinion: A number of metabolic pathways will be explored in future years, and many of these pathways are potential therapeutic targets and may serve as diagnostic and prognostic biomarkers of ccRCC.