Itraconazole (ITZ), a broad-spectrum triazole antifungal agent, exhibits remarkable pharmacodynamic and pharmacokinetic properties. However, the low solubility of ITZ significantly reduces its oral bioavailability. Furthermore, it has been reported that this medication can result in dose-related adverse effects. Therefore, the objective of this study was to enhance the solubility of ITZ through the utilization of various polymers and to manufacture personalized and programmable release ITZ tablets. Five different polymers were selected as water-soluble carriers. Thirty percent / ITZ was mixed with seventy percent / of the polymers, which were then extruded. A series of physical and chemical characterization studies were conducted, including DSC, PXRD, PLM, and in vitro drug release studies. The results demonstrated that ITZ was dispersed within the polymers, forming ASDs that markedly enhanced its solubility and dissolution rate. Consequently, soluplus was employed as the polymer for the extrusion of ITZ-loaded filaments, which were subsequently designed and printed. The in vitro drug release studies indicated that the release of ITZ could be regulated by modifying the 3D structure design. Overall, this study found that the combination of HME and 3D printing technologies could represent an optimal approach for the development of personalized and precise drug delivery dosages.