Non-coding RNAs (ncRNAs) regulate antitumor immunity but clinical use is hindered by instability, poor specificity, and immunogenic risk. Lipid nanoparticles (LNPs) offer a promising delivery solution due to biocompatibility, a modifiable surface, and efficient ncRNA encapsulation. Preclinical and early clinical studies have demonstrated the efficacy of LNP-ncRNA therapies in various cancers, including respiratory, digestive, and neurologic malignancies, and in cancer immunotherapy. This review evaluates engineered LNPs administered via different routes, explains the mechanisms that promote antitumor effects, and highlights advances in overcoming delivery barriers to enhance immunotherapy. Current limitations of engineered LNPs are also analyzed, essential translational challenges are identified, and future directions to facilitate the clinical application of LNP-based ncRNA therapies are suggested.