The metabolomics approach, defined as the study of all endogenously-produced low-molecular-weight compounds, appeared as a promising strategy to define new cancer biomarkers. Information obtained from metabolomic data can help to highlight disrupted cellular pathways and, consequently, contribute to the development of new-targeted therapies and the optimization of therapeutics. Therefore, metabolomic research may be more clinically translatable than other omics approaches, since metabolites are closely related to the phenotype and the metabolome is sensitive to many factors. Metabolomics seems promising to identify key metabolic pathways characterizing features of pathological and physiological states. Thus, knowing that tumor metabolism markedly differs from the metabolism of normal cells, the use of metabolomics is ideally suited for biomarker research. Some works have already focused on the application of metabolomic approaches to different cancers, namely lung, breast and liver, using urine, exhaled breath and blood. In this Special Issue we contribute to a more complete understanding of cancer disease using metabolomics approaches.