Constructed wetland systems (CWSs) can offer cost-effective wastewater treatment in developing countries like Pakistan. This study focused on optimizing design and operational parameters of CWSs in horizontal surface flow (HSF), vertical surface flow (VSF), and hybrid mesocosms for treating sewage and textile effluents using local hydrophytes: Lemna minor, Typha latifolia, and Eichhornia crassipes. Pollutants and heavy metals (Cd, Cr, Cu, Pb, Ni, and Zn) were removed under different flow configurations, bedding materials, hydrophyte species, and hydraulic retention times (HRT) to optimize the overall contaminant removal efficiency (RE). Key findings indicated that the hybrid CWS achieved a maximum RE of 63.62% for total suspended solids (TSS) and 57.9% for biochemical oxygen demand (BOD) at an HRT of 3 days, with efficiencies declining at longer retention times. Additionally, the hybrid system showed maximum metal removal, with Cd and Cr RE reaching 75.2% and 70.5%, respectively. The study also highlighted the critical role of hydrophyte species and HRT in optimizing RE. Furthermore, the choice of hydrophyte species significantly influenced pollutant removal, with treatment cells containing mixed hydrophytes achieving the highest removal efficiencies (63.62%), followed by Eichhornia crassipes with high Cd (643.33 mgkg⁻¹) and Cr (1103.72 mgkg⁻¹) uptake. A lower HRT of 3 days resulted in the highest overall removal efficiency of 57.5%, which decreased with longer HRTs (from 6 to 9 days). Optimizing design and operational parameters is crucial for maximizing CWS treatment potential.