With the ongoing advancement of immune checkpoint research, targeting tumors through immune checkpoint blockade has emerged as a crucial approach in cancer therapy. T cell immunoglobulin and mucin-domain containing protein 3 (TIM-3) functions as a negative immune checkpoint. It has been demonstrated that the interaction of TIM-3 with its ligand galectin-9 (Gal-9) can promote immune escape in a variety of cancers. In hematologic, digestive, and respiratory tumors, it affects different signaling pathways by blocking TIM-3/Gal-9 interaction, thereby regulating the growth of T cells, B cells, dendritic cells, NK cells, and monocytes/macrophages, and inhibiting regulatory T cells to exert anti-tumor effects. TIM-3 antibodies have potential therapeutic value as immune checkpoint inhibitors in molecularly-targeted anti-tumor therapy. This article reviews the mechanisms of anti-tumor effects of TIM-3/Gal-9 in the tumor microenvironment of various cancers.