Pheochromocytomas and paragangliomas (PPGLs) are highly variable with respect to clinical presentation, endocrine phenotype, growth rate and metatastatic potential. This relates to a large genetic diversity and related pathways of tumorigenesis. By applying a multi-omics approach, profound abnormalities in tumor cell metabolism related to mitochondrial defects in a subset of PPGLs have been identified. Metabolic profiling of PPGL tumor tissues can be achieved by several techniques, including proton nuclear magnetic resonance spectroscopy and liquid chromatography- mass spectrometry. The underlying genotypes affect tumor cell metabolism beyond the Krebs cycle, impacting on purine/pyrimidine and amino acid metabolism, energy storage and oxidative stress response. Besides investigation of tumor tissues, metabolic profiling of PPGLs in patients can also be achieved non-invasively by 18F-fluorodeoxy glucose positron emission tomography and proton magnetic resonance spectroscopy. These in- and ex-vivo metabolomic approaches hold great promise for individual tumor characterization, thereby guiding tailor-made diagnostic and therapeutic strategies.