Rapid population growth and mass migration from rural to urban centers have contributed to a new era of water sacristy, and a significant drop in per capita freshwater availability, resulting in the reuse of wastewater emerging as a viable alternative. The reuse of wastewater after treatment using the soil aquifer treatment (SAT) has recently gained popularity due to low operating/maintenance cost of the method. However, the presence of organic micropollutants (OMPs) may present a health risk if the SAT is not adequately designed to ensure required attenuation of the OMPs. An important aspect of the design of the SAT system is the large degree of natural variability in the OMP concentrations/loads in the wastewater and the uncertainty associated with the current methods for calculation of the removal efficiency of the SAT for theOMPs. This study presents a novel model for more accurate prediction of the removal efficiency of the SAT system for the OMPs and the fate of the OMPs trapped within the vadose zone. A large data set is compiled covering a broad range of aquifer conditions, and the SAT system parameters, including hydraulic loading rate and dry/wet ratio. This study suggests that removal of OMPs in SAT systems is most affected by biodegradation rate and soil saturated hydraulic conductivity, in addition to dry to wet ratio. This conclusion is reached by the application of the developed prediction model using data sets from the case study SAT systems in Egypt.