Cancer immunotherapy holds great potential to battle cancer by exerting a durable immunity effect. However, this process might be limited by various constraints existing in the tumor microenvironment (TME), such as the lack of available neoantigen, insufficient T cells from the naive repertoire, or immunosuppressive networks in which immunogenic tissue is protected from immune attacks. Certain chemotherapeutic drugs could elicit immune-potentiating effects by either inducing immunogenicity or relieving tumor-induced immunosuppression. Some also leave tumors directly susceptible to cytotoxic T cell attacks. Mounting evidence accumulated from preclinical and clinical studies suggests that these two treatment modalities might be mutually reinforcing as an effective "chemo-immunotherapy" strategy. Herein, we reviewed the latest advances in cancer immunotherapy and related mechanisms involved in chemotherapeutic-mediated immune activation. The emerging combination strategies and synergistic effects in response to chemo-immunotherapy are highlighted. We also discuss the challenges and critical considerations in its future development.