Cancer is a refractory disease, which brings physical, mental and economic sufferings on patients and their families. The activation of oncogenes and/or the deletion of tumor repressors result in uncontrolled tumor survival and proliferation. Therapeutic resistance and cancer recurrence are common issues during the course of clinical treatment. Since each single treatment can’t eradicate tumor cells completely, the development of combinatorial therapeutic regimen is in the spotlight for several decades. Combinatorial therapeutic regimen, a treatment modality that combines two or more therapeutic agents, targets key pathways in a characteristically synergistic or an additive manner. It aims to improve the efficacy and magnitude of therapeutic responses and reduce the likelihood of acquired resistance by using optimal drug dose with tolerable side effect. Currently, the combinatorial therapeutic regimen not only includes various chemicals, but also diverse therapeutic modalities which affected DNA damage repair, protein localization and degradation, post-translational modification, cell metabolism and apoptosis, as well as immune response.