A spray tower was used to strip the water vapor from the dilute solutions in this study. The role of each operating parameter and its relationship in this stripping/regeneration (ST/RE) process are still unknown. To improve the ST/RE process and elucidate the relationship between the process variables, an experimental design methodology was used to evaluate the process variables of the ST/RE process. A second-order polynomial model with a multiple linear regression to estimate the model coefficients of the five selected factors (process variables) was proposed to study the influence of the factors on the mass transfer coefficient response in the ST/RE process. Only 32 (or 2(5)) experimental runs were necessary to assess these variables and the model satisfied the process very well since the coefficient of determination (R-2) was very close to one. The analysis of the mass transfer performance with these experimental data was also reported in this study.