Cells constantly adjust their metabolic state in response to extracellular signals and nutrient availability to meet their demand for energy and building blocks. Recently, there has been significant research into the metabolic aspects of embryonic stem cells/pluripotent stem cells (ESCs/PSCs) and cancer stem cells (CSCs), which has revealed the unique metabolic status of different stem cell lineages. While ESCs and CSCs were largely thought to harbor similar metabolic states, recent evidence demonstrates that their metabolic dependency is distinctly different. The glucose metabolism of ESCs largely depends on glycolysis, including a one-carbon pathway during differentiation. While proliferating cancer cells share the glycolytic phenotype of ESCs, the mitochondria-centric oxidative phosphorylation constitutes an important metabolic circuit of CSCs under metabolic stress, indicating the dynamic nature of metabolic plasticity. In this review, we catalogued metabolic signatures of cellular "stemness" to provide insights into the therapeutic potential of ESCs and CSCs.