Metabolomics is one of the newcomers among the "omics" techniques, perhaps also constituting the most relevant for the study of pathophysiological conditions. Metabolomics may indeed yield not only disease-specific biomarkers but also profound insights into the etiology and progression of a variety of human disorders. Various metabolomic approaches are currently available to study oncogenesis and tumor progression in vivo, in murine tumor models. Many of these models rely on the xenograft of human cancer cells into immunocompromised mice. Understanding how the metabolism of these cells evolves in vivo is critical to evaluate the actual pertinence of xenograft models to human pathology. Here, we discuss various tumor xenograft models and methods for their metabolomic profiling to provide a short guide to investigators interested in this field of research.