Metabolism supports the biosynthetic and energetic demand of all living creatures. Over decades, we have accumulated knowledge of how individual enzymes work in vitro, but we don’t have a good sense about how they work together in vivo. Thus, fundamental to our understanding of metabolic operation is the ability to measure metabolic activity in vivo. In this talk I will first briefly introduce an optical imaging technique that allows visualization of metabolism at micron scale. And then I will show how we use multi omics to probe metabolism at a systems scale. By quantifying hundreds of molecular components, these systems-level measurements allow us to gain fundamental metabolic design principles. For example, an important metabolic decision is whether to generate energy through fermentation or respiration. Respiration is much more energy efficient. Nevertheless, many fast-growing cells, including the baker’s yeast, activated T cells, and tumor cells, switch to aerobic glycolysis (fermentation in the presence of oxygen). How do they achieve the metabolic switch? Why would they prefer wasteful metabolism?  I hope you will join the journey with me to explore the plasticity of metabolism.