This work presents the study of the thickness vs. stiffness relationship for different materials (PMMA and PEEK) in patient-specific cranial implants, as a criterion for the selection of biomaterials from a mechanical perspective. The geometry of the implant is constructed from the reconstruction of the cranial lesion using image segmentation obtained from computed axial tomography. Different design parameters such as thickness and perforations are considered to obtain displacement distributions under critical loading conditions using finite element analysis. The models consider quasi-static loads with linear elastic materials. The null hypothesis underlying this research asserts that both biomaterials exhibit the minimum mechanical characteristics necessary to withstand direct impact trauma at the implant center, effectively averting critical deformations higher than 2 mm. In this way, the use of PMMA cranioplasties is justified in most cases where a PEEK implant cannot be accessed.