The abscopal effect refers to the regression of metastatic cancer at distant sites not directly irradiated by radiotherapy, which is thought to be mediated by the immune system. However, this effect is rare due to immune tolerance mechanisms. Recent research suggests that combining radiotherapy with immunotherapy can enhance the abscopal effect, extending its application to both local and metastatic disease. This review discusses the mechanisms behind the abscopal effect, the role of immunotherapy in boosting it, and the challenges in achieving consistent results. It also explores current and potential cross-disciplinary approaches, including the use of smart materials to address these challenges. Radiotherapy is a key component of cancer treatment, but its effectiveness is limited by toxicity and the need for precise targeting. Advances in radiotherapy technologies, such as intensity-modulated radiation therapy (IMRT), image-guided radiotherapy (IGRT), and proton therapy, have improved therapeutic ratios and reduced toxicity. These technologies, combined with immunotherapy, may enhance the abscopal effect by stimulating immune responses against cancer cells. The abscopal effect is mediated by immune cells, particularly CD8+ T cells, which recognize and attack both primary and metastatic tumors. However, immunosuppressive factors, such as TGF-β and MDSCs, can hinder this response. Strategies to overcome immunosuppression include using immunotherapy agents like anti-CTLA4 and anti-PD1, which can enhance T cell activity. Additionally, smart materials, such as nanoparticles and smart radiotherapy biomaterials, offer potential for targeted delivery of immunotherapeutic agents, improving efficacy and reducing toxicity. Combining radiotherapy with immunotherapy has shown promise in clinical trials, with some studies reporting abscopal responses in up to 30% of patients. However, challenges remain in optimizing dosing, timing, and delivery methods to maximize the abscopal effect while minimizing side effects. Ongoing research aims to refine these combinations and explore new approaches, including the use of smart materials, to improve treatment outcomes for patients with cancer. The integration of immunotherapy with radiotherapy represents a promising avenue for enhancing cancer treatment and improving patient survival.The abscopal effect refers to the regression of metastatic cancer at distant sites not directly irradiated by radiotherapy, which is thought to be mediated by the immune system. However, this effect is rare due to immune tolerance mechanisms. Recent research suggests that combining radiotherapy with immunotherapy can enhance the abscopal effect, extending its application to both local and metastatic disease. This review discusses the mechanisms behind the abscopal effect, the role of immunotherapy in boosting it, and the challenges in achieving consistent results. It also explores current and potential cross-disciplinary approaches, including the use of smart materials to address these challenges. Radiotherapy is a key component of cancer treatment, but its effectiveness is limited by toxicity and the need for precise targeting. Advances in radiotherapy technologies, such as intensity-modulated radiation therapy (IMRT), image-guided radiotherapy (IGRT), and proton therapy, have improved therapeutic ratios and reduced toxicity. These technologies, combined with immunotherapy, may enhance the abscopal effect by stimulating immune responses against cancer cells. The abscopal effect is mediated by immune cells, particularly CD8+ T cells, which recognize and attack both primary and metastatic tumors. However, immunosuppressive factors, such as TGF-β and MDSCs, can hinder this response. Strategies to overcome immunosuppression include using immunotherapy agents like anti-CTLA4 and anti-PD1, which can enhance T cell activity. Additionally, smart materials, such as nanoparticles and smart radiotherapy biomaterials, offer potential for targeted delivery of immunotherapeutic agents, improving efficacy and reducing toxicity. Combining radiotherapy with immunotherapy has shown promise in clinical trials, with some studies reporting abscopal responses in up to 30% of patients. However, challenges remain in optimizing dosing, timing, and delivery methods to maximize the abscopal effect while minimizing side effects. Ongoing research aims to refine these combinations and explore new approaches, including the use of smart materials, to improve treatment outcomes for patients with cancer. The integration of immunotherapy with radiotherapy represents a promising avenue for enhancing cancer treatment and improving patient survival.