Ionizing radiation (IR) is traditionally known for its cytotoxic effects on cancer cells by causing DNA damage, leading to cell death. However, recent evidence suggests that IR also modulates the immune system, enhancing its potential as a cancer treatment. This review explores the dual role of IR in cancer therapy: as a direct cytotoxic agent and as an immune modulator. The effects of different types and doses of IR on the immune system, particularly immune cell activation, cytokine production, and immune surveillance, are discussed. The review also examines the negative impacts of IR on the immune system and the potential of combining IR with immunotherapies to improve clinical outcomes. Mechanisms such as macrophage activation, dendritic cell function, and cytotoxic T lymphocyte response to IR are analyzed, highlighting IR’s ability to enhance antigen presentation and immune cell polarization. Additionally, the influence of IR on various cell signaling pathways, including the cGAS-STING and NLRP3 inflammasome pathways, is reviewed, emphasizing their roles in immune enhancement and tumor immunity. The potential of IR to be integrated with other immunotherapies for more effective cancer treatment is underscored.