<p>Nanotechnology-based drug delivery systems have significantly advanced modern pharmaceutics by addressing limitations associated with conventional therapies, including poor solubility, rapid systemic clearance, and nonspecific drug distribution. Among various nanocarriers, liposomes remain one of the most clinically validated platforms due to their biocompatibility, structural similarity to biological membranes, and capacity to encapsulate both hydrophilic and lipophilic drugs. Despite extensive research, important translational challenges persist, including formulation stability, variability in tumor targeting via the EPR effect, manufacturing scalability, and immunogenicity associated with repeated dosing. This review provides an integrated and critical overview of liposome-based drug delivery systems, combining mechanistic insights, formulation design principles, preparation technologies, and clinical translation perspectives within a single framework. Particular emphasis is placed on recent advances in liposomal engineering <b>strategies,</b> including surface modification, stimuli-responsive systems, and scalable manufacturing approaches such as microfluidics. Clinically established formulations such as Doxil® and AmBisome® are highlighted as representative examples demonstrating improved therapeutic efficacy and reduced toxicity compared with conventional formulations. In addition, the review discusses emerging trends in next-generation liposomal systems, including targeted liposomes, RNA-delivery platforms, and hybrid lipid–polymer vesicles. By integrating formulation science with translational considerations and recent developments (2022–2025), this review provides an updated perspective on the evolving role of liposomes in nanomedicine and highlights key directions for future research and clinical development.</p> Graphical Abstract <p></p>