Radiation therapy is used in about 60 percent of cancers for either curative or palliative purposes, and the response to radiation by individual patients is influenced by both tumor-intrinsic and tumor-extrinsic factors. Specific features of the tumor microenvironment can affect tumor oxygenation and certain metabolic pathways, leading to radiation resistance. Other pathways can modulate both the tumor microenvironment and distant microenvironments, leading to therapeutic resistance and distant metastases. Understanding and targeting these pathways may lead to novel strategies to enhance the efficacy of radiation therapy in solid tumors at the individual level, and possibly open the way to novel radiotherapy-drug combinations. Three researchers explored the potential of these novel strategies during an American Association for Cancer Research (AACR) Annual Meeting 2023 symposium on Monday, April 17. The session, Radiation Therapy, DNA Damage, and Immune Response, can be viewed on the virtual meeting platform by registered Annual Meeting participants through July 19, 2023.