The above-knee amputation is a common challenge and has been increasing in recent times due to accidents, chronic infections and aging. Therefore, it is very important to investigate and characterize biocompatible materials and femur bone replacement and implantation to tackle bone amputation challenges. This research used theoretical and numerical approaches to investigate the compatibility of different biomaterials which are commercially pure titanium metal (CP Ti), magnesium alloy (AZ31) and Polymethyl methacrylate (PMMA) for the implantation of the femur bone, and the propertied critical load, contact pressure, critical stress, the natural frequency with different modes, and fatigue life were determined. Materialise interactive medical imageing control system software was used to create a three-dimensional model of the human femur bone based on CT scan data and the volumetric mesh was created with 3-MATIC software. The bone material property was determined through apparent density and allocated for different regions of femur bone based on hounsfield unit value, and homogenization was done using DIGIMAT software. The prosthesis bone plate and the hip joint were designed according to the specifications proposed by the TIPSAN catalogue, ASTM F2996-13 and ISO 7206-4:2010(E) standards. The results showed that for total femur replacement and implantation at the interface by AZ31 material, the natural frequency was 38% and 15% higher than the natural femur bone respectively, whereas for an implant with total hip replacement CP Ti was better with 22% higher natural frequency than the natural femur bone. For all implants; total femur replacement, implant at the interface and total hip replacement, CP Ti was 197.65kN, 35kN and 36kN which are 90%, 54% & 55.36% higher weight carrying capacity than natural femur bone respectively and PMMA material was 0.16284Mpa, 0.41654Mpa and 0.25941Mpa which are 60%, 2.2% & 57% lower in contact pressure than natural femur bone respectively. The fatigue life of 1.0042 * 10 6 and energy absorption for femur bone replaced by AZ31 material were higher than that of CP Ti, PMMA and natural femur bone life. The RSM response shows for higher body weight increment, the critical load for femur bone replaced by AZ31 material was obtained to be 30.4 kN and 14 kN for CP Ti. KeyWords: Femur bone; Biocompatibility; Numerical modeling; Implant; MIMICS.