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Recently, there is a huge volume of polluted wastewater released from the industries, which adversely affects the environment and human health. As a result, finding a simple, inexpensive, and efficient strategy for water purification is one of the major concerns of researchers. In this study, based on the scope of heavy metals removal from the polluted water, the polymer inclusion membrane has been employed for Co(II) removal. In this way, the main separation parameters in the membrane structure and aqueous phases including carrier percentage, percentage of plasticizer, pH of source phase, and receiving phase acid concentration have been considered at the room temperature and atmospheric pressure, simultaneously, by applying the response surface methodology. The range of considered parameters varied between 5 and 35%wt (total weight of the reference membrane), 40-70%wt (total weight of the reference membrane), 2.5-6.5, and 0.5-2.5 mol L -1 for the carrier percentage, percentage of plasticizer, pH of the source phase, and receiving phase acid concentration, respectively. The statistical analysis of experimental tests showed an admissible agreement between these values and model outputs by developing acceptable results for Adj-R 2 (0.9978) and p-value (p < 0.0001). Also, the ion removal has been optimized by maximizing the removal factor at a constant time of 24 h (%RF max = 73.25%) to achieve the optimum quantities of considered parameters. A test in the optimal operational conditions with the removal factor of 73.99% verified the reliability and accuracy of the proposed model. Finally, the interaction coefficients between the considered variables are completely analyzed to have a better grasp about the polymer inclusion membranes.