The hallmark of tumor microenvironment is that it makes up of numerous immunomodulatory cells and factors which exert essential roles in immunoprotection and immunosuppression in addition to tumor cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells reported to promote immunosuppression and angiogenesis and facilitate tumor metastasis and invasion. The wide scope of MDSCs functional activities make these cells promising targets for effective cancer treatments. In this review, we briefly discuss the origin, subpopulation, and functions of MDSCs, as well as the potential to target these cells for therapeutic benefit. We focus on the underlying molecular mechanisms of these drugs targeting MDSCs, mainly from the standpoint of molecules related to drug targets.