The introduction of additive manufacturing (AM) technologies has profoundly revolutionized the implant manufacturing industry, with a particularly significant impact on the field of orthopedics. Electron Beam Melting (EBM) and Direct Metal Laser Sintering (DMLS) represents AM fabrication techniques with a pivotal role in the realization of complex and innovative structure starting from virtual 3D model data. In this study, Ti–6Al–4V and Co–Cr–Mo materials, developed by EBM (Ti-POR) and DMLS (Co-POR) techniques, respectively, with hydroxyapatite (Ti-POR + HA; Co-POR + HA) and type I collagen (Ti-POR-COLL; Co-POR-COLL) coatings, were implanted into lateral femoral condyles of rabbits. Osseointegration process was investigated by histological, histomorphometrical and microhardness evaluations at 4 and 12 weeks after implantation. Both Ti–6Al–4V and Co–Cr–Mo implants, with or without HA and COLL coatings, demonstrated good biocompatibility. As expected, HA coating hastened bone-to-implant contact (BIC) process, while collagen did not significantly improved the osseointegration process in comparison to controls. Regarding newly trabecular bone formation (B.Ar/T.Ar), Co-POR presented the highest values, significantly different from those of Co-POR-COLL. Over time, an increase of BIC parameter and a decrease of B.Ar/T.Ar were detected. Higher mineral apposition rate was observed for Ti-POR and Co-POR in comparison to Ti-POR-COLL and Co-POR-COLL, respectively, at 12 weeks. The same behavior was found for bone formation rate between Co-POR and Co-POR-COLL at 12 weeks. In conclusion, the AM materials guarantee a good osseointegration and provide a suitable environment for bone regeneration with the peculiarity of allowing personalized and patient-specific needs customization to further improve the long-term clinical outcomes.