The treatment of wastewater containing azo dyes, a primary textile industry effluent, is strongly governed by the dyes’ chemical properties. Herein, the decolorization efficiency and operating costs of electro-oxidation (EO) using Pt/Ti electrodes and conventional chemical coagulation (CC) for treating synthetic wastewater containing either Azo Reactive Red 196 (ARR196) or Azo Disperse Red 153 (ADR153) were investigated. Operational parameters—including initial dye concentration (Ci, dye), applied current intensity (IC), and wastewater feeding rate (F) for EO; and Ci, dye, aluminum sulfate dose (CAl), and initial pH for CC—were optimized via the response surface methodology (RSM). The results indicate that dye structure and solubility significantly influence treatment efficiency and operating costs, as statistically confirmed via ANOVA for quadratic model predictions (p < 0.05 and R2 values) for both EO and CC processes. Conventional CC was most effective for the low-solubility ADR153, achieving a 97% removal efficiency at a low operating cost of 0.03 USD/m3, compared to 57.5% at 0.15 USD/m3 for ARR196. In contrast, EO was superior for the highly soluble ARR196, achieving an 83.3% decolorization efficiency at 0.024 USD/m³, whereas ADR153 exhibited only 64.2% decolorization efficiency at a substantially higher operating cost of 1.63 USD/m³. IC and F were the critical factors (p<0.05) for the EO process, while pH was the primary determinant for CC. This study identified a direct correlation between specific chemical characteristics of pollutants and treatment efficiency, highlighting the necessity of selecting treatment technologies based on pollutant types to strategically optimize both economic and environmental outcomes.