<p>Over the past few decades, numerous biological therapeutics, such as RNAs and polypeptides, have emerged as promising alternatives to traditional chemotherapy. While their molecular mechanisms of action are well-understood, their clinical application remains hindered by several critical barriers, including inherent intracellular instability, the need for precise target-site delivery, poor cellular uptake, and immune system clearance. To overcome these challenges, the development of selective delivery systems has been raised as an indispensable strategy. Among various drug carriers, cationic lipid-based platforms have garnered significant attention and are increasingly exploited in oncology. This review summarizes the physicochemical characteristics of cationic lipid-based nanoparticles and evaluates various therapeutic cargos based on their biological properties. Furthermore, we explore the current research applications and clinical potential of these nanoparticles in cancer treatment.</p>