Tannery wastewater effluent (TWE) consists of a variety of complex structured compounds having very low biodegradability. Few attempts have been made to treat real-time TWE consisting of complex compounds and find the intermediate compounds formed during the HC+PAA+ FeSO4.7 H2O treatment system. Therefore, a pilot scale study has been conducted on an orifice-embedded hydrodynamic cavitation reactor for treating real-time TWE. Liquid chromatography-high resolution mass spectrometry (LC-HRMS) has been carried out to identify the specific compounds present in TWE before and after treatment. Response surface methodology (RSM) – Box-Behnken design (BBD) obtained maximum COD, TDS and turbidity removal efficiency of 72.36%, 94.54% and 98.89%, respectively, at cavitation time-97.5 min, inlet pressure-7.5 bar, pH-2, orifice diameter-0.5 mm, PAA dosage-17.5 g/L, and PAA /FeSO4.7 H2O-2:1 ratio. The reaction rate constant was increased from 2.455 × 10−3 to 12.75 × 10−3 min−1 when AOPs were combined with HC. The study concluded that the degradation using HC+PAA+ FeSO4.7 H2O successfully increased the biodegradability of the TWE without forming any toxic by-products.