Introduction: Cranial defects resulting from trauma, tumors, surgical procedures, and congenital conditions, necessitate effective prosthetic solutions to restore both form and function. This study aims to design and evaluate a cranial prosthesis using advanced CAD techniques, and a biocompatible coating for enhanced mechanical properties and to promote osteointegration. Materials and Methods: Tomographic images of a patient with cranial decompression were reconstructed in 3D Slicer and used to design the prosthesis using software CAD: Rhino, and SolidWorks. Finite element analysis in SolidWorks assessed mechanical performance. Displacement and tension testing of the impact area were conducted. Furthermore, a prototype was 3D printed in PLA to evaluate the quality of the design and dimensions. Finally, hydroxyapatite was synthesized hydrothermally with microwave assistance and characterized for future coating applications of our cranial prosthesis. Results: Finite element analysis confirmed the prosthesis’ mechanical integrity and validated the prosthesis's mechanical performance under displacement and tension. The 3D-printed prototype exhibited accurate replication of the defect site. Hydroxyapatite coating displayed a high degree of purity and crystallinity, favorable conditions for osseointegration, and mechanical resistance. Conclusion: The integrated approach successfully yielded a cranial prosthesis prototype with optimized mechanical properties and biocompatibility. Utilization of tomographic imaging reconstructed in 3D Slicer, CAD design, 3D printing, and mechanical testing offers a comprehensive solution for cranial defect restoration, promising improved patient outcomes and quality of life.