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This study examines the removal efficiency of Tramadol hydrochloride (TR) and mineralization (chemical oxygen demand, COD) by the effective photoinduced Fenton-simulated system under artificial light (UVA). The Box-Behnken design was used to optimize the value of each parameter. The model yielded the following optimal parameters: [TR]0 = 10 mg, ratio ([Oxalate ]0/[Fe3+]0) = 100, initial pH = 2.83, and [Fe3 +]0 = 1.298 mg with effective TR removal (100%) and COD removal efficiency (72.82%). The presence of oxygen has a positive effect by increasing hydrogen peroxide production from 4.36 to 8.12 mg L−1 and by maximizing a change in Fe3+ speciation. The degradation kinetics of ΤR in the oxygen-saturated medium is four times faster than that in the normal aerated medium. The Kapp rate constants increased quickly from 5.72 × 10−2 to 20 × 10−2min−1. The percent COD removal increased to 87.46%, and the final pH increased from 5.31 to 6.23.