Novel drug delivery systems (NDDS) have dramatically transformed the pharmaceutical landscape, offering innovative approaches to enhance the efficacy, safety, and patient compliance of therapeutic agents. These advancements include nanotechnology-based systems, polymeric carriers, targeted delivery mechanisms, and controlled release formulations. Each of these systems addresses specific challenges associated with traditional drug delivery methods, such as poor bioavailability, rapid degradation, and systemic side effects. Nanotechnology-based systems, including nanoparticles, liposomes, dendrimers, and nanosuspensions, offer precise targeting and improved drug stability. Polymeric drug delivery systems, such as hydrogels and microspheres, provide controlled and sustained release of drugs, enhancing therapeutic outcomes. Targeted drug delivery systems, like ligand-targeted delivery and antibody-drug conjugates (ADCs), ensure that drugs are delivered specifically to diseased cells, minimizing off-target effects. Controlled release systems, through mechanisms like diffusion, degradation, and osmosis, maintain therapeutic drug levels over extended periods, improving patient adherence. These innovative systems have found applications across various medical fields, including oncology, infectious diseases, neurological disorders, and cardiovascular diseases. The integration of emerging technologies, such as 3D printing and personalized medicine, further enhances the potential of NDDS. This comprehensive review explores the different types of novel drug delivery systems, their mechanisms, clinical applications, and future perspectives, highlighting the significant impact of these technologies on modern medicine. Through ongoing research and collaboration, NDDS will continue to evolve, offering more effective, precise, and patient-centered therapeutic solutions.