Altered tissue mechanics and metabolism are defining characteristics of cancer that impact not only proliferation but also migration. While migrating through a mechanically and spatially heterogeneous microenvironment, changes in metabolism allow cells to dynamically tune energy generation and bioenergetics in response to fluctuating energy needs. Physical cues from the extracellular matrix influence mechanosignaling pathways, cell mechanics, and cytoskeletal architecture to alter presentation and function of metabolic enzymes. In cancer, altered mechanosensing and metabolic reprogramming supports metabolic plasticity and high energy production while cells migrate and metastasize. Here, we discuss the role of mechanoresponsive metabolism in regulating cell migration and supporting metastasis as well as the potential of therapeutically targeting cancer metabolism to block motility and potentially metastasis. Altered mechanical cues within the tumor microenvironment impact migration and metabolism, where crosstalk between mechanosignaling and metabolism supports metabolic plasticity and high energy production during metastasis. In this review, Zanotelli and Zhang et al. discuss the role of bioenergetics in migration and mechanoresponsive metabolism in regulating cancer invasion and metastasis.