This paper addresses the interception mission of hypersonic vehicles by weapon defense systems. A simulation model of the attack-defense confrontation process is constructed based on the “F2T2EA” kill chain model. Building upon this framework, a novel method combining TOPSIS, the entropy weight method, and fuzzy theory is proposed, guided by the concept of kill chain closure, to evaluate the interception effectiveness of defense systems against boost-glide hypersonic vehicles. The model’s effectiveness is verified through practical examples, with consistent conclusions obtained through traditional grey correlation analysis, thus confirming the feasibility and reliability of both the model and the evaluation methodology. The results of this research offer reliable technical support for the design and combat application of defense systems and provide a reference for future optimization efforts.