Recent years have witnessed the dramatic improvement of nanoparticle‐mediated radiotherapy in preclinical or even clinical cancer research. Among the extensive developments, tumor‐targeted strategies are receiving more and more attention as they become able increase their therapeutic effects as well as reduce the side effects to healthy tissues. The tumor microenvironment (TME) with its critical function in tumor development and distinctive abnormal characteristics, is also widely studied as a target/response for tumor‐specific nano‐radiotherapy. The fast advances of TME‐assisted nano‐radiotherapy have offered numerous novel strategies and approaches for efficiently destroying cancer. This review summarizes the recent advances and development of TME‐enabled nanoparticle‐mediated radiotherapy. Firstly, a brief description of the typical TME characteristics including vasculature, hypoxia, mild acidity, redox reactions, extracellular matrix, and various cellular components is given. Next, the representative examples of TME‐enabled nanoparticle‐mediated radiotherapy are categorized and discussed in two parts: TME components–targeted nano‐radiotherapy and TME characteristics‐responsive nano‐radiotherapy. Lastly, some obstacles and challenges associated with this field are also proposed at the end of this review.