Tumor necrosis factor receptor 2 or TNFR2 is considered as an appealing target protein due its limited frequency to Tregs which are highly immunosuppressive and its presence on human malignancies. Numerous studies have revealed that TNFR2 is primarily found on MDSCs (myeloid derived suppressor cells) and CD⁺Foxp3⁺ regulatory T cell (Tregs). It has a great importance in the proliferation and functional activity of Tregs and MDSCs. To treat malignancies and diseases like autoimmune disorder, the suppressor activity of TNFR2 must be eliminated by downregulation or upregulation. Therefore, at the molecular level, advances in comprehension of TNFR2's complex structure and its binding to TNF have opened the door to structure-guided drug development. Two key obstacles of cancer treatment are the dearth of Treg-specific inhibitors and the lack of widely applicable ways to directly target tumors via frequently expressed surface oncogenes. Many researchers have discovered potential antagonist and agonist of TNFR2 which were successful in the inhibition of Tregs proliferation, reduction of soluble TNFR2 secretion from normal cells and in the expansion of T effector cells. The representation of the data in the following review article elucidates the clinically administrated TNFR2 antagonist and agonist in the treatment of cancers.