Background: Maxillofacial bone defects present considerable challenges in oral and reconstructive surgery. While autologous bone grafts are the gold standard, their limitations, such as donor site morbidity and limited availability, have driven the search for alternative biomaterials. SmartBone^®, a xeno-hybrid graft, offers potential advantages due to its bioactivity and remodeling capacity. Methods: This analysis of a series of clinical cases, evaluated the performance of SmartBone^® in 10 patients presenting with various maxillofacial bone defects. The patient follow-up period spanned from 2017 to 2019, with a maximum duration of 30 months. Bone grafting was performed, and integration was monitored using Cone-Beam Computed Tomography at multiple timepoints. Bone density changes (ΔCT values) in selected anatomical sites were analyzed to assess graft transformation and integration. Results: SmartBone^® supported effective bone regeneration and selective remodeling in all cases. One patient required a revision procedure, after which successful integration was observed. Cellular colonization began within weeks, with complete remodeling into mature bone occurring between 6–12 months. Evidence of cortical wall resorption and reformation on the graft’s external surface confirmed this transformation. ΔCT values progressively aligned with native bone densities, indicating structural and functional integration. Conclusions: SmartBone^® demonstrates strong osteointegrative and site-specific remodeling capabilities, offering a reliable and predictable alternative for maxillofacial bone reconstruction. The study presents several limitations, including the small sample size, inter-patient variability, possible imaging artifacts due to metallic elements in Cone-Beam Computed Tomography scans and the lack of histological confirmation.