The coastal area of the Mekong Delta is facing a huge problem of water supply quality due to pesticide (intensive agriculture) and salinity (sea water intrusion) contamination. Their simultaneous presence makes this water complex and requires advanced water treatment processes in order to meet the Vietnamese Guideline for drinking water quality. The objective of this work is to develop an efficient surface water treatment based on electrodialysis and nanofiltration technologies. The approach consists in using electrodialysis in a first stage for salinity removal to improve, in the second stage, the performance of nanofiltration for the removal of pesticides. The question that arises is to what extent should electrodialysis desalination be carried out in order to effectively remove the pesticide and salinity in the second stage (nanofiltration) at a reasonable cost? To answer this question, an experimental design methodology was employed to describe and optimize the entire hybrid system. Experiments carried out under the optimal conditions deduced from the modeling gave experimental results in good agreement with the predictions allowing to validate the optimization approach.