Radiation therapy against cancer frequently fails to attain the desired outcomes because of several restricting aspects. Radiation therapy is not a targeted antitumor treatment, and it poses serious threats to normal tissues as well. In many cases, some inherent features of tumors make them resistant to radiation therapy. Several nanoparticles have shown the capacity to upgrade the viability of radiation treatment because they can directly interact with ionizing radiation to increase cellular radiation sensitivity. Several types of nanomaterials have been investigated as radio-sensitizers, to improve the efficacy of radiotherapy and overcome radio-resistance including, metal-based nanoparticles, quantum dots, silica-based nanoparticles, polymeric nanoparticles, etc. Despite all this research and development, certain challenges associated with the exploitation of nanoparticles to enhance and improve radiation therapy for cancer treatment are encountered. Potential applications of nanoparticles as radiosensitizers is hindered by the difficulties associated with ensuring their production at a large scale with improved characterizations and because of certain biological challenges. By overcoming the shortcomings of nanoparticles like working on the pharmacokinetics, and physical and chemical characterization, the therapy can be improved. It is expected that in the future more knowledge will be available regarding nanoparticles and their clinical efficacy, leading to the successful development of nanotechnology-based radiation therapies for a variety of cancers. This review highlights the limitations of conventional radiotherapy in cancer treatment and explores the potential of nanotechnology, specifically the use of nanomaterials, to overcome these challenges. It discusses the concept of using nanomaterials to enhance the effectiveness of radiation therapy and provides an overview of different types of nanomaterials and their beneficial properties. The review emphasizes the need to address the obstacles and limitations associated with the application of nanotechnology in cancer radiation therapy for successful clinical translation.