The development of long-lasting zirconia-based ceramics for implants, which are not prone to hydrothermal aging, is not satisfactorily solved. Therefore, this study is conceived as an overall evaluation screening of novel ceria-stabilized zirconia-alumina-aluminate composite ceramics (ZA8Sr8-Ce11) with different surface topographies for use in clinical applications. Ceria-stabilized zirconia is chosen as the matrix for the composite material, due to its lower susceptibility to aging than yttria-stabilized zirconia (3Y-TZP). This assessment is carried out on three preclinical investigation levels, indicating an overall biocompatibility of ceria-stabilized zirconia-based ceramics, both in vitro and in vivo. Long-term attachment and mineralized extracellular matrix (ECM) deposition of primary osteoblasts are the most distinct on porous ZA8Sr8-Ce11p surfaces, while ECM attachment on 3Y-TZP and ZA8Sr8-Ce11 with compact surface texture is poor. In this regard, the animal study confirms the porous ZA8Sr8-Ce11p to be the most favorable material, showing the highest bone-to-implant contact values and implant stability post implantation in comparison with control groups. Moreover, the microbiological evaluation reveals no favoritism of biofilm formation on the porous ZA8Sr8-Ce11p when compared to a smooth control surface. Hence, together with the in vitro in vivo assessment analogy, the promising clinical potential of this novel ZA8Sr8-Ce11 as an implant material is demonstrated.