Insight into the metabolic reprogramming of cancer cells provides not only an understanding of the biology of the tumor but also novel biomarkers for diagnosis, prognosis, and therapy response monitoring. Cellular differentiation of tumors can be characterized by enhanced glycolysis, which is in accordance with changes in mitochondrial function and nutritional utilization. Elevated blood lactate and some amino acids have also been linked to tumor malignancy and unfavorable prognosis. Recent technologies, such as magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), have advanced the detection of metabolic biomarkers. These methodologies enable the comprehensive metabolic profiling of tumor tissues and body fluids, which can identify specific metabolites with the potential to be used as biomarkers. In addition, the combination of genomics and proteomics with metabolomics has offered enhanced insights into cancer metabolism and has revealed the potential for the discovery of new therapeutic targets. They have also recognized the possibility of employing noninvasive imaging methods, such as positron emission tomography using radioactively labeled metabolites, to image tumor metabolism in real time. Such imaging modalities have the potential for delivering dynamic images of metabolic events occurring during treatment and offer a potent tool for monitoring treatment response and adapting the treatment plan accordingly. This book chapter discusses the status of cancer metabolic biomarkers and their discovery from the laboratory to clinical application potential.