Solid tumors reside in harsh tumor microenvironments (TMEs) together with various stromal cell types. During tumor progression and metastasis, both tumor and stromal cells undergo rapid metabolic adaptations. Tumor cells metabolically coordinate or compete with their “neighbors” to maintain biosynthetic and bioenergetic demands while escaping immunosurveillance or therapeutic interventions. Here, we provide an update on metabolic communication between tumor cells and heterogeneous stromal components in primary and metastatic TMEs and discuss emerging strategies to target metabolic communications for improved cancer treatments. Growing solid tumors consist of malignant cancer cells and heterogeneous stromal cell components. This Review from Simon and Li provides an updated overview of metabolic communication between tumor cells and stromal cells in primary and metastatic tumor microenvironments and discusses emerging strategies to target metabolic interactions for improved cancer therapies.