This review explores the emerging role of aptamers in enhancing radiotherapy (RT) efficacy through their ability to target tumor sites with high specificity. Cancer, a complex disease, involves uncontrolled cell growth, and radiosensitization refers to the process of making cancer cells more sensitive to radiation therapy. As versatile carriers, aptamers facilitate the delivery of radiosensitizing agents such as nanoparticles, siRNAs, and therapeutic molecules. These conjugates modulate cell signaling, enhance free radical production, and influence the tumor microenvironment (TME) via immunomodulatory mechanisms, thereby indirectly increasing tumor radiosensitivity. Key findings highlight aptamer-based strategies for disrupting critical pathways, boosting immune responses, and overcoming tumor resistance. Advances in multi-agent and liposomal delivery systems further underscore their potential to address tumor heterogeneity and immune evasion. This review consolidates recent developments, emphasizing aptamers' role as precise delivery vehicles for optimizing RT outcomes and advancing cancer treatment.