Myeloid derived suppressor cells (MDSCs) represent a population of heterogeneous myeloid cells that are at early stages of development. There is an accumulation of MDSCs in tumor microenvironment. The generation of MDSCs can counteract T cell responses. Generation, expansion and playing a role in promoting tumor of the MDSCs rely on signaling pathways such as STAT3, IL-1β/NF-κB, PI3K/AKT/mTOR, PGE2/Cox2 and RAS. Perturbation of signaling pathways involved during normal hematopoietic and myeloid development, leading to the generation and accumulation of suppressive MDSCs and immunosuppressive tumor microenvironment. Targeting these pathways should help in elucidating mechanisms that lead to the expansion of MDSCs in cancer and point to methods for eliminating these cells from the tumor microenvironment, especially the STAT3 signaling pathway.