Background: Biodegradable polymeric nanoparticles have emerged as a promising platform for enhancing cancer therapy by enabling targeted drug delivery to tumor sites. The ability to manipulate the chemical and physical properties of these polymers allows them to overcome various biological barriers and achieve site-specific drug accumulation. Objectives: This research focused on the development and optimization of chitosan nanoparticles loaded with doxorubicin hy drochloride using the ionic gelation method for targeted and controlled delivery in cancer therapy. Methods: Chitosan nanoparticles were prepared using the ionic gelation method with sodium tripolyphosphate (TPP) as the crosslinking agent. Formulation parameters, including chitosan to TPP ratio, drug to polymer ratio, and mixing conditions, were systematically optimized. The prepared nanoparticles were characterized for particle size, polydispersity index (PDI), zeta po tential, surface morphology, entrapment efficiency, drug loading capacity, and in vitro drug release behavior at pH 5.5 (tumor microenvironment) and pH 7.4 (physiological conditions). Results: The optimized formulation demonstrated a mean particle size of 142.6 ± 3.8 nm with a narrow PDI of 0.124 ± 0.021, indicating a highly monodisperse population. The zeta potential was measured as +22.4 ± 1.6 mV after chitosan coating, con firming excellent colloidal stability. Encapsulation efficiency reached 87.3 ± 2.6% with a drug loading capacity of 7.2 ± 0.3%. In vitro release studies revealed a biphasic sustained release profile with enhanced release at acidic pH (5.5), confirming the pH sensitive nature of the chitosan-based delivery system. The formulation exhibited rapid reconstitution within 22 seconds and maintained a physiologically compatible pH of 6.8. Conclusion: The optimized chitosan nanoparticles demonstrated controlled drug release with enhanced release at acidic pH, confirming the pH-sensitive nature of the chitosan-based delivery system. This research establishes a foundation for developing effective chitosan-based nanocarriers for targeted cancer chemotherapy.