RNA-based therapeutics have been explored for a broad spectrum of applications, with clinical and FDA-approved drugs targeting diseases including dystrophies, systemic diseases, viruses, and cancer [1], [2], [3], [4]. In particular, its utility in tumor immunotherapy has surged, spanning in vitro and preclinical in vivo testing, as well as clinical trials. Broadly, cancer immunotherapies manipulate the systemic and local immune system to reactivate anti-tumor response, overriding intrinsic escape and immune-avoidance mechanisms of the tumor [5]. However, despite the merits of the immunotherapies that include agonist antibodies, checkpoint inhibitors, and adoptive cellular therapies, clinical success has been limited by factors including immunotherapy-associated toxicities [6] and unpredictable efficacy [7]. Targeting these limitations, studies on RNA-mediated therapy have demonstrated both improved tumor targeting and systemic clearance, leading to its rise in recognition, passing pre-clinical testing to gain clinic utility. In this review, we will discuss RNA therapeutics as well as their delivery vehicles and routes, with a particular focus on lipid-based nanoparticles. We will also summarize the challenges faced and provide discussion on the future of RNA-based cancer immunotherapy.