Background: The treatment of soft tissue vascular anomalies is a challenge in materials science, requiring injectable biomaterials that can conform to complex lesion architectures while providing controlled drug delivery. Conventional liquid sclerosants fail due to poor localization. This study reports on the formulation and clinical performance of an in situ-forming, drug-eluting composite foam designed to overcome these limitations. Methods: A multicomponent composite foam was formulated from a liquid phase containing bleomycin and polidocanol and a gaseous phase of room air using a standardized Tessari emulsification technique. The therapeutic performance of this composite was evaluated retrospectively in 14 patients with high-risk airway venous malformations (AVMs) by quantifying lesion volume reduction on magnetic resonance imaging (MRI) and assessing clinical outcomes. Biocompatibility was determined by monitoring adverse tissue reactions. Results: The injectable composite foam demonstrated superior clinical performance with a 100% therapeutic response rate. Full target lesion ablation, defined as a complete response, was achieved in 10 of 14 cases (71.4%), demonstrating the composite’s high efficacy. The material exhibited excellent biocompatibility, with adverse events limited to minor, localized mucosal necrosis (21.4%) that resolved without intervention, indicating predictable material-tissue interaction. Conclusions: The bleomycin-polidocanol composite foam is an effective, therapeutic biomaterial whose performance is directly linked to its unique physicochemical structure. This work validates a material-based strategy for treating complex vascular lesions and highlights the potential for further optimization of such injectable composites by enhancing their long-term stability.