Hybrid nanostructures combine organic and inorganic materials to create efficient drug delivery platforms. These systems overcome limitations of conventional nanoparticles by leveraging synergistic properties of composite elements. This review covers design principles, synthesis methods, and clinical applications in drug delivery and therapy. These nanomaterials exhibit enhanced encapsulation efficiency, improved bioavailability, and superior biocompatibility. Classification into Category I (non-covalent) and Category II (covalent) systems enables rational design strategies. Therapeutic applications span cancer chemotherapy, gene therapy, infectious disease management, and diagnostic imaging. Targeting strategies using passive and active mechanisms significantly enhance efficacy. Despite manufacturing and clinical translation challenges, emerging trends in artificial intelligence- guided design and personalized medicine offer promising directions.