Proteomics and metabolomics offer a nonbiased suite of tools to address pathophysiologic mechanisms from various levels by integrating signal transduction, cellular metabolism, and phenotype analysis. To link alterations of cellular proteins to metabolism and function, we have recently combined proteomic and metabolomic techniques. Examples, including genetic manipulation, ischemic preconditioning, atherosclerosis, and stem cell differentiation, are discussed to illustrate how the combination of these updated technologies may advance our understanding of cardiovascular biology.