Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of myeloid cells with immature phenotypes and immunosuppressive functions. This population of cells has been extensively studied over the past decade owing to an increasing recognition of their pivotal role in pathological conditions including cancers, infectious diseases, sepsis, and autoimmune diseases. Various treatments targeting MDSCs are currently under development or in clinical trials with the aim to restore functional immunity against tumors or pathogens. Recent advances in immune metabolism demonstrate the role of metabolic pathways, especially lipid metabolism, in the differentiation and function of MDSCs in tumor environments. Therefore, a comprehensive understanding of lipid metabolism in MDSCs would facilitate the development of novel therapies against tumors through metabolic reprograming of MDSCs.