Orthopedic implants should have sufficient strength and promote bone tissue regeneration. However, most conventional implants are optimized for use either under high mechanical load or for active osseointegration. To achieve the dual target of mechanical durability and biocompatibility, polyether ether ketone (PEEK) filaments reinforced with internal titanium dioxide (TiO2) nanoparticles via dopamine-induced polymerization are additively manufactured into an orthopedic implant through material extrusion (ME). The exterior of the PEEK/TiO2 composite is coated with hydroxyapatite (HA) using radiofrequency (RF) magnetron sputtering to increase both the strength and biocompatibility provided by homogeneous ceramic–ceramic interactions and the protuberant nanoscale topography between the internal TiO2 nanoparticle reinforcement and external HA coating. The hardness, tensile, and compression, and scratch test results demonstrate a considerable enhancement in the mechanical strength of the hierarchical PEEK/TiO2/HA hybrid composite structure compared to that of the conventional 3D-printed PEEK. Furthermore, PEEK with internal TiO2 reinforcement improves the proliferation and differentiation of bone cells in vitro, whereas the external HA coating leads to a more prevalent osteoblast absorption. Micro-computed tomography and histological analyses confirm new bone formation and a high bone-to-implant contact ratio on the HA-coated PEEK structure reinforced with TiO2 nanoparticles.