This paper examines the technical and economic feasibilities of the sequential optimization technique, i.e., Taguchi coupled with principal component analysis (PCA). Fenton oxidation with four operating parameters, such as [Dye](ini), Dye/Fe+2 (wt/wt), H2O2/Fe+2 (wt/wt), and pH, was selected as a case study. COD (%), TOC (%), and color removal efficiency were chosen as responses. Total principal component index (TPCI) values, obtained as an output of sequential optimization, were used to determine the optimized conditions for Fenton oxidation. [Dye]: 100 mg/L, Dye/Fe+2(wt/wt): 50, H2O2/Fe+2(wt/wt): 25 and pH: 3 were obtained as the optimized values. In addition, ANOVA and the interaction of factors showed that pH was the most significant factor with the percent contribution of 90.86%. Economic evaluation with simultaneous comparison with Taguchi and central composite design (CCD) showed that Taguchi coupled with PCA is the most economic and time-efficient optimization technique. In this study, experimental cost was reduced to $ 54/m(3), which showed 95% reduction relative to CCD. Moreover, chemical consumption and experimental time were also reduced by approximately 95-97% and 68%, respectively. Thus, it can be concluded that Taguchi coupled with PCA is the most cost-effective and less-laborious way of optimizing multi-response processes such as Fenton oxidation.