This research focuses on developing a novel ultra high molecular weight polyethylene (UHMWPE) material reinforced with titanium dioxide (TiO 2 ) nanoparticles for producing craniofacial prostheses via an incremental sheet forming process (SPIF). First, UHMWPE-TiO 2 nanocomposite sheets were produced using incipient wetting and the compression molding process by considering different concentrations of TiO 2 nanoparticles. Then, the influence that the compression molding fabrication process has on the crystallinity and structural properties of the produced sample sheets was investigated. Experimental characterizations via scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared (FT-IR), tensile mechanical testing, and live/dead cell viability assays provided data that show an enhancement of the physical, mechanical, and biological properties. Finally, modifications on the nanocomposite material properties due to the SPIF manufacturing processes of a craniofacial prosthesis are addressed.