Background: Polymethyl methacrylate (PMMA) resin is extensively utilized in prosthodontics and orthodontics, particularly in fabricating artificial teeth, provisional crowns, denture bases, and orthodontic retainers. Aims: This study aimed to evaluate the effects of incorporating cerium oxide and polyether ether ketone nanoparticle (CP) composite into PMMA resin on transverse strength, impact strength, surface hardness, and denture base adaptation. Materials and Methods: A total of 120 PMMA specimens were divided into three groups based on the concentration of CP composite added to PMMA resin, with each group consisting of 40 specimens: a control group without fillers, group (A) containing 1% wt. of composite filler with a ratio of 30% cerium oxide and 70% polyether ether ketone, and group (B) comprising 3% wt. of composite with a ratio of 50% ceria, and 50% polyether ether ketone, as determined by the pilot study. Each group was tested for transverse strength, impact strength, surface hardness, and denture base adaptation, with 10 specimens for each test. The tested specimens were examined using Fourier transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (FE–SEM). The resulting data were statistically analyzed using SPSS at a significance level of P≤0.05.  Results: Group B showed a significant statistical increase in transverse and impact strength compared with the other groups. Surface hardness and denture adaptation increased significantly in group A. FTIR analysis revealed transmission peaks and heightened intensity after the addition of the CP composite into the PMMA. The FE–SEM images showed a well-distributed nano CP composite within the PMMA matrix for all experimental groups, with increased agglomeration observed in group B (3%). Conclusion: The incorporation of 3% wt. CP into PMMA resin significantly improved transverse and impact strength compared with 1% wt. and the control. The surface hardness and denture base adaptation improved when 1% wt. CP was incorporated into the PMMA resin compared with the other tested groups.