While the response surface method is an effective method in engineering optimization, its accuracy is often affected by the use of limited amount of data points for model construction. In this chapter, the issues related to the accuracy of the RS approximations and possible ways of improving the RS model using appropriate treatments, including the iteratively re-weighted least square (IRLS) technique and the radial-basis neural networks, are investigated. A main interest is to identify ways to offer added capabilities for the RS method to be able to at least selectively improve the accuracy in regions of importance. An example is to target the high efficiency region of a fluid machinery design space so that the predictive power of the RS can be maximized when it matters most. Analytical models based on polynomials, with controlled level of noise, are used to assess the performance of these techniques.