Addressing non-unions involves stabilizing the affected area through osteosynthesis and improving bone biology using bone grafts. However, there is no consensus on the optimal treatment method. This study aims to compare outcomes of non-union surgery using conventional treatment methods (metal hardware ± graft) versus osteosynthesis with the human allogeneic cortical bone screw (Shark Screw®) alone or in combination with a metallic plate. Thirty-four patients underwent conventional treatment, while twenty-eight cases received one or more Shark Screws®. Patient demographics, bone healing, time to bone healing, and complications were assessed. Results revealed a healing rate of 96.4% for the Shark Screw® group, compared to 82.3% for the conventionally treated group. The Shark Screw® group exhibited a tendency for faster bone healing (9.4 ± 3.2 vs. 12.9 ± 8.5 weeks, p = 0.05061). Hardware irritations led to six metal removals in the conventional group versus two in the Shark Screw® group. The Shark Screw® emerges as a promising option for personalized non-union treatment in the foot, ankle, and select lower leg cases, facilitating effective osteosynthesis and grafting within a single construct and promoting high union rates, low complications, and a rapid healing process.