This comprehensive study designed polymeric nanoparticles of itraconazole and evaluated the properties and performance of Itraconazole-loaded polymeric nanoparticles, focusing on their formulation, stability, and release kinetics. The integrity of itraconazole within the nanoparticles was validated by Fourier Transform Infrared Spectroscopy (FT-IR) analysis, which revealed no appreciable chemical changes after encapsulating. Drug release rates and bioavailability are directly impacted by drug/polymer ratios, as demonstrated by the differences in particle sizes that were found through investigation. Zeta potential measurements showed that the presence of negative surface charges prevented aggregation, resulting in adequate stability. The entrapment efficiency of several formulations was also evaluated in the study; some showed excellent efficiency, indicating ideal formulation circumstances. Studies on the release of drugs in vitro showed controlled release profiles that were noticeably better than those of the pure drug, indicating increased therapeutic efficacy. The formulation's capacity to increase itraconazole's bioavailability—a critical factor for medications with poor solubility—was further validated by solubility testing. The formulation's potential to enhance absorption across various intestinal segments was highlighted by ex vivo intestinal permeability experiments. Studies on stability revealed that the mixture remained more stable at lower temperatures, which has important storage and handling implications.