SUMMARY The DRC Regional Metabolomics and Fluxomics Core at Princeton provides Penn DRC investigators with access to state-of-the-art metabolomics and flux analysis. These capabilities allow DRC investigators to measure, both broadly and quantitatively, metabolic activity in cell culture, animal model, and clinical specimens relevant to diabetes and obesity. Usage is high, at about 5000 samples annually. Scientific impact has also been high, with 34 DRC publications as a Primary Core, including Cell, Science, Nature x 2, Journal of Clinical Investigation x 2, Nature Metabolism x 3, and Cell Metabolism x 7. This impact reflects the intellectual synergies between the Core’s expertise in quantitative metabolomics and isotope tracing and DRC member expertise in diabetes and obesity. In the coming five years, the Core will continue to provide world-class Metabolomics and Lipodomics measurements with and without isotope labeling. It will also continue to assist Users with experimental design and data interpretation and to advance methods to meet User needs. In addition, the Core will introduce new capacity in Spatial Metabolomics and Fluxomics based on MALDI imaging mass spectrometry. The goal is to enable Users to make measurements of key diabetes-relevant metabolites and fluxes in tissue slices with single-cell spatial resolution. Access to these capabilities will both accelerate and expand the horizons of DRC science, leading to improved diagnosis and treatment of diabetes, obesity, and related disorders.