Complex bone defects continue to pose significant challenges in the field of orthopedics, where the restoration of structural integrity and the promotion of osteointegration are essential for successful repair outcomes. Three-dimensional (3D) printing offers a robust approach for the fabrication of patient-specific scaffolds with precise architectural and functional control. In this study, we designed and fabricated porous scaffolds composed of tantalum and titanium alloys, both exhibiting identical porosity, utilizing 3D printing technology. We conducted a systematic comparison of their mechanical properties, in vitro osteogenic potential, and in vivo bone integration within a defect model. The porous tantalum scaffolds demonstrated exceptional biocompatibility, enhanced cell adhesion, and significantly promoted the osteogenic differentiation of mesenchymal stem cells as well as extracellular matrix mineralization. In vivo, the porous tantalum scaffolds not only expedited bone repair but also improved osteoconductive ingrowth compared to their titanium counterparts. Omics analyses further elucidated potential biological mechanisms underlying the superior performance of porous tantalum. These findings underscore the potential of 3D-printed porous tantalum as a promising scaffold material for the clinical repair of bone defects.