Recent research trends show interest inovercoming the limitations of wastewater treatment systems and technologies. More researchers are investigating ecologically friendly, low-cost, and low-maintenance alternatives. More focus is being placed on environmentally friendly and sustainable treatment techniques as a result of the growing population and increasing industrialization, which have increased the pollution load on receiving water bodies from both point and non-point sources. Because of its effectiveness, affordability, and sustainability, the phytoremediation process is among the greatest ways to remediate wastewater. The system's advantages and response surface methodology (RSM) are used in this work to make predictions. This process is important for enhancing the efficiency of pollutant removal from wastewater. Phytoremediation uses plants to absorb, degrade, or stabilize contaminants, offering a sustainable and low-cost solution. RSM provides a powerful statistical tool to optimize key operational parameters, identify significant factors, and model the treatment process accurately. Two different plants were placed in phytoremediation system tanks to treat wastewater treatment plant's effluent. Water hyacinth and Salvinia molesta were planted in separate tanks and observed concurrently. The pH and hydraulic retention time (HRT) of the tanks were varied during operation. The results revealed that the removal efficiency of chemical oxygen demand, total dissolved solids, total nitrogen, and turbidity were in the range of 51.84-79% for Salvinia molesta with pH 5, and 52.12-83% with pH7. Water hyacinth recorded lower performances of 13.56-48.81% and 5.29-44.87%, respectively. Accurate predictions were made from the analysis of phytoremediation treatment of wastewater utilizing the response surface approach. Integrating RSM with phytoremediation improves the effectiveness and predictability of effluent treatment.