Nanocomposites containing polymers, hydroxyapatite, and carbon nanotubes have shown great potential for orthopedic applications. However, the synthesis process selected significantly impacts the properties and performance of these nanocomposites. Our study described here investigated the effects of various synthesis methods on the mechanical and structural characteristics of functionalized Multi-Walled Carbon Nanotubes/Polyetheretherketone/Hydroxyapatite (f-MWCNT/PEEK/HAp) hybrid nanocomposites. Our primary objective was to comprehensively understand the many synthesis strategies that could be employed to customize these materials for orthopedic purposes. Several synthesis methods were explored by the authors to produce homogeneous nanocomposites with uniform dispersion and good interfacial bonding. Chemical solution blending, selective chemical solution blending, and three-dimensional mechanical mixing are all examples of such techniques. The produced nanocomposites were tested for crystallinity, tribological properties and molecular compositions using X-ray diffraction (XRD), tribological testing and Fourier transform infrared (FTIR) spectroscopy methods. This study demonstrated different synthesis methods for an orthopedic-targeted hybrid nanocomposite material. The hybrid nanocomposite’s formulation was changed to enhance the material’s properties. The composite was composed of polyetheretherketone (PEEK), hydroxyapatite (HAp) and functionalized multi-walled carbon nanotubes (f-MWCNT). The outstanding tribological performance of the generated nanocomposite was ensured by including the f-MWCNT and HAp in the PEEK.