Over the years, nanotechnology has gained popularity as a viable solution to address gene and drug delivery challenges over conventional methods. Extensive research has been conducted on nanosystems that consist of organic/inorganic materials, drugs, and its biocompatibility become the primary goal of improving drug delivery. Various surface modification methods help focus targeted and controlled drug release, further enabling multidrug delivery also. This newer technology ensures the stability of drugs that can unravel the mechanisms involved in cellular processes of disease development and its management. Tailored medication delivery provides benefits such as therapy, controlled release, and reduced adverse effects, which are especially important for controlling illnesses like cancer. However, multifunctional nanocarriers that possess high viscoelasticity, extended circulation half-life, biocompatibility, and biodegradability face some challenges and limitations too in human bodies. To produce a consistent therapeutic platform based on complex three-dimensional nanoparticles, careful design and engineering, thorough orthogonal analysis methods, and reproducible scale-up and manufacturing processes will be required in the future. Safety and effectiveness of nano-based drug delivery should be thoroughly investigated in preclinical and clinical trials, especially when considering biodistribution, targeting specific areas, and potential immunological toxicities. Overall, the current review article explores the advancements in nanotechnology, specific to nanomaterial-enabled drug delivery systems, carrier fabrication techniques and modifications, disease management, clinical research, applications, limitations, and future challenges. The work portrays how nanomedicine distribution affects healthcare with an emphasis on the developments in drug delivery techniques.