Radiotherapy (RT) is an important and effective cancer treatment method clinically. In the tumor microenvironment (TME), RT can induce tumor-specific immune responses by infiltrating immune cells throughout the body, such as T cells, dendritic cells (DCs), and natural killer cells (NK cells), and induce distant tumor regression. However, it can also increase some immune suppressor cells including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and tumor-associated neutrophils (TANs), leading to radiation resistance. This can result in the effectiveness of RT being limited by immune suppression in the TME. Recently, new immunotherapy approaches have been demonstrated can block immune suppression and restore anti-tumor immunity. With help of nanomedicine, immunoadjuvants can be efficiently delivered to TME for blocking immune suppression to improve RT and immunotherapeutic function. This review systematically summarizes the changes of T/B cells, TAMs, NK cells, DCs, MDSCs, TANs in TME after RT and discusses the strategies of nanomedicine-mediated RT and immunotherapy combination treatment. Overall, the combination of nanomedicine-mediated RT and immunotherapy represents a promising cancer treatment method. It has the potential to improve the effectiveness of cancer therapy and benefit patients in the future.