A continuous system of moving bed biofilm reactor (MBBR) integrated with horizontal subsurface flow constructed wetland (HSSFCW) followed by a sedimentation tank (PUMBBR-CW) was used for the removal of chemical oxygen demand (COD), ammonia (NH4+), and paracetamol. The removal performance of the reactor was analyzed by varying the initial concentration of the pollutants, hydraulic retention time (HRT), and COD to NH4+ ratio (C/N ratio). Polyurethane foam (PUF) waste was used as the bio-carrier in the MBBR system. Microbial degradation, plant uptake, and substrate adsorption were the most dominant removal mechanisms in the PUMBBR-CW. Further insights into the degradation mechanisms were investigated by characterizing the substrate and bio-carrier and analyzing the degradation by-products. More than 95 % of COD removal was achieved with 30.6 h HRT and 550 mg/L initial concentration at a C/N ratio of 10. At 30.6 h HRT and a C/N ratio of 4, 87 % NH4+ and 94 % paracetamol removal were achieved. The low C/N ratio favors paracetamol removal, as the microorganism uses paracetamol as the sole carbon source under low C/N conditions. Moreover, it was found that paracetamol was uptake and stored in the Canna indica L. plant leaves (216 µg/g). An artificial neural network (ANN) was developed to find the optimum operating condition with maximum removal efficiency. The PUMBBR-CW system effectively overcame the drawbacks of conventional wastewater technologies, such as high footprint, variable pollutant loads, and high maintenance. Hence, it can be used as a highly efficient method of treating wastewater.