Metastasis is the process by which cancer cells from the primary tumor travel through the blood stream to generate a secondary tumor site in a distant organ. Although very few cells are able to make this journey, the resulting effects are dire since most cancer fatalities are due to the presence of metastatic lesions. Therefore, understanding the mechanisms by which cells metastasize can help uncover vulnerabilities and facilitate the development of novel strategies for preventing and/or combatting metastatic cancer. Here, we investigated the metabolic features of a rare population of plastic and stem-like cells in breast cancer called metastasis-initiating cells (MICs) that are highly efficient at colonizing distant organs. We found that endogenous MICs rely on mitochondrial metabolism, specifically the tricarboxylic acid cycle (TCA) and fatty acid usage. Sorting tumors cells based solely on mitochondrial activity or levels of neutral lipid stores is sufficient at identifying MICs. We determined that in MICs, the TCA cycle is important for generating citrate that is then exported out to the cytoplasm for the regeneration of acetyl-CoA and subsequent acetylation of H3K27. Blocking acetyl-CoA generating metabolic pathways and readers of H3K27ac reduced expression of epithelial-to-mesenchymal related genes, MIC frequency, and metastatic capacity. In contrast, supplying an exogenous source of acetyl-CoA, reverses these effects. In breast cancer patient cohorts, we also observe a correlation between heightened expression of our MIC-derived metabolic signature and acetyl-CoA generating enzymes with distant relapse-free survival or overall survival. These suggest that there is a complex interplay between metabolism and epigenetics that induces and maintains a pro-metastatic phenotype in breast cancer cells. Metastasis is a systemic disease that arises from the confluence of optimally balanced multimodal inputs. It is therefore no surprise, that current efforts to target late-stage metastatic cancers with monotherapies leave much to be desired. It may therefore be worthwhile to determine an ideal synergistic combination of therapies that targets several MIC-dependencies simultaneously to effectively prevent or eradicate metastatic disease and lower the chances of compensatory resistance mechanisms, while reducing the likelihood of toxic adverse effects.