The overall performance of an Air Defense Missile System (ADMS), identified as the probability of hit (PoH) performance, is evaluated using full grid analysis approach and response surface approach. For this purpose, a very detailed six degrees of freedom missile simulation model is employed, which contains over 1000 parameters. These parameters are varied with prescribed uncertainties for performing Monte-Carlo runs to estimate the PoH of a hypothetical missile. Although such a high-fidelity model is necessary for performance analysis, the analysis process is usually very time consuming and can be computationally expensive. In this paper, a response surface method, based on an experimental design, is generated using fundamental parameters that affect PoH. Engagement downrange and altitude, and seeker lock-on-range of the missile are selected as the fundamental inputs. Sampling points related to conventional uniform grid and response surfaces in the experimental design are analyzed. The number of Monte-Carlo simulations at each point is determined. The response surfaces are constructed, and their results are compared with uniform grid analysis results. It is shown that the response surface models represent the performance of the domain accurately alleviating the need for full gird analysis, thereby reducing the computational load substantially.