The existing wavelet-based image resolution enhancement techniques have many assumptions, such as limitation of the way to generate low-resolution images and the selection of wavelet functions, which limits their applications in different fields. This paper initially identifies the factors that effectively affect the performance of these techniques and quantitatively evaluates the impact of the existing assumptions. An approach called Optimal Factor Analysis employing the genetic algorithm is then introduced to increase the applicability and fidelity of the existing methods. Moreover, a new Figure of Merit is proposed to assist the selection of parameters and better measure the overall performance. The experimental results show that the proposed approach improves the performance of the selected image resolution enhancement methods and has potential to be extended to other methods.