The integration of Computer-Aided Drug Design (CADD) tools with nanotechnologies has enhanced the era of drug discovery, drug delivery systems, research and development. CADD tools, including its major approaches; structure-based drug design (SBDD) and ligand-based drug design (LBDD), streamlining the process of Hit identification, lead optimization, and validation of novel therapeutic agents. These in silico methods aid to the rational drug design by predicting their molecular interactions with biological targets, thus enhancing the efficiency and accuracy of the basic steps in the drug discovery process. Nanotechnology, with its unique properties such as high surface-area-to-volume ratio and tunable surface chemistry, provides pioneering solutions for targeted drug delivery, improving the bioavailability and therapeutic index of drugs. The synergy between CADD tools; such as pharmacophore modeling and molecular dynamic simulations, with nanotechnology not only fast-tracks the drug discovery process but also boosts the accuracy and efficiency of targeted drug delivery, paving the way for innovative therapeutic solutions. This chapter explores the applications of CADD tools in the design and development of nanotechnology-based drug delivery systems, reviewing hot advancements, challenges, and future perspectives in this interdisciplinary field.