3D printing of pharmaceutical formulations requires juggling between the material properties and the printing process to achieve the geometry of the 3D printed products with the desired dose and release. The purpose of the current investigation is to identify the material suitability for semisolid extrusion-based 3D printing of advanced drug delivery system. In this study, the semisolid extrusion-based 3D printing technique was optimized to print a controlled release shell as a vehicle/carrier for oral drug delivery system. The consistency of the printable paste was optimized by screening different solvents for the polymer of interest (cellulose acetate as optimum) to achieve the desired continuous and uniform extrudability behavior. The polarity of the solvent played important role in the selection of the suitable solvent for the optimization process. The nozzle shape (tapered tip as optimum) and the nozzle diameter (630 µm as optimum) were found to be also significantly influenced by extrusion behavior. The printing pressure (60 psi) and speed (4 mm/s) were optimized to reach the required rate of extrusion during the 3D printing process. The thickness and the width of the printed layers have contributed to the creation of the standard triangle language (STL) G-code for the printing of the 3D drug delivery system. It was found that the first printed layer deposited on a particular type of substrate plays a significant role to influence the spreadable behavior of extruded materials. Finally, the present study design proposes a rational guideline for the semisolid extrusion-based 3D printing of pharmaceutical products of specific interest for personalized medicine.