The fruitful results of tumor immunotherapy establish its indispensable status in the regulation of the tumorous immune context. It seems that the treatment of programmed cell death receptor 1 (PD-1) blockade is one of the most promising approaches for cancer control. The significant efficacy of PD-1 inhibitor therapy has been made in several cancer types, such as breast cancer, lung cancer, and multiple myeloma. Even so, the mechanisms of how anti-PD-1 therapy takes effect by impacting the immune microenvironment and how partial patients acquire the resistance to PD-1 blockade have yet to be studied. In this review, we discuss the cross talk between immune cells and how they promote PD-1 blockade efficacy. In addition, we also depict factors that may underlie tumor resistance to PD-1 blockade and feasible solutions in combination with it.