Cancer immunotherapy and nucleic acid therapy have demonstrated significant potential in reshaping cancer treatment paradigms. The combination of these therapeutic approaches offers promising prospects for enhancing systemic anti-tumor effects while minimizing adverse reactions commonly associated with traditional treatments. However, the clinical efficacy of these innovative therapies is often hindered by several delivery-related challenges. These include issues like degradation of therapeutic molecules, limited cellular uptake, the essential requirement for nuclear entry, and risks of off-target toxicity that can negatively impact patient safety. In this challenging landscape, nanoparticle delivery systems, particularly lipid nanoparticles (LNPs), have emerged as a groundbreaking solution to overcome these obstacles. LNPs facilitate the safe and efficient delivery of nucleic acid therapy directly to immune cells, enhancing their bioavailability and therapeutic impact. This review article examines the evolving role of LNPs in the landscape of cancer immunotherapy. Recent advancements in LNP-based nucleic acid delivery illustrate their potential to revolutionize the field by enabling precise modulation of gene expression and immune responses, paving the way for improved cancer treatment outcomes and providing a more effective arsenal against this complex disease.