Over the past decade, numerous studies have attempted to enhance the effectiveness of radiotherapy (external beam radiotherapy and internal radioisotope therapy) for cancer treatment. However, the low radiation absorption coefficient and radiation resistance of tumors remain major critical challenges for radiotherapy in the clinic. With the development of nanomedicine, nanomaterials in combination with radiotherapy offer the possibility to improve the efficiency of radiotherapy in tumors. Nanomaterials act not only as radiosensitizers to enhance radiation energy, but also as nanocarriers to deliver therapeutic units in combating radiation resistance. In this review, we discuss opportunities for a synergistic cancer therapy by combining radiotherapy based on nanomaterials designed for chemotherapy, photodynamic therapy, photothermal therapy, gas therapy, genetic therapy, and immunotherapy. We highlight how nanomaterials can be utilized to amplify antitumor radiation responses and describe cooperative enhancement interactions among these synergistic therapies. Moreover, the potential challenges and future prospects of radio-based nanomedicine to maximize their synergistic efficiency for cancer treatment are identified.