Targeting Toll-like receptors 7 and 8 (TLR7/8) has emerged as a promising strategy in cancer immunotherapy. TLR7/8 agonists activate robust Th1-type immune responses and bridge innate and adaptive immunity. Further, TLR7/8 agonists can serve as valuable adjuncts to conventional therapies, such as chemotherapy and radiotherapy, enhancing efficacy while reducing adverse effects. Their integration into combination regimens for cancer offers a dual advantage: amplifying antitumor immunity and reducing tumor burden. Notably, the incorporation of TLR7/8 agonists into cancer vaccine platforms has yielded encouraging results in preclinical models and is advancing toward clinical application. This review highlights the mechanisms of action, therapeutic potential, and recent progress in the development of TLR7/8 agonist-based strategies for cancer treatment. We also discuss ongoing clinical evaluations and the rationale for combining these agents with existing modalities to enable more effective, personalized, and accessible cancer therapies.