In this work, the estimation capacity of the response surface methodology (RSM), in the catalytic naphtha reforming to enhance the octane number of reformats via isomerization reaction pathway and minimize the aromatization activity over tri-metallic modified Pt-Re/Al2O3 catalyst were investigated by applying Design of experiment (DOE). The parent bimetallic catalysts were modified using a relatively inactive metal (Sn) by means of employing non-conventional method of anchoring technique called controlled surface reaction (CSR) method in order to favor the intimate contact of Sn with the active phase to suppress the metallic character of Pt metal. The correlations between RON, aromatization and isomerization activities with three reaction variables namely temperature (480-510 o C), pressure (10-30 bar) and space velocity LHSV (1.2-1.8 h-1) were presented as empirical mathematical models via reforming of a complex mixture (80 o C-185 o C). Numerical results indicated that the minimum aromatization activity was 20% when reaction temperature was 460 o C and pressure of 35 bar. Results also show that maximum isomerization activity of 58% was achieved when pressure is 30 bar and space velocity is 1.8 h. it has been found that optimum value of RON = 89 was attained at 449.9 o C, 32 bar and 1.7 h-1. However, high operating pressure and low reaction temperature significantly decrease the aromatization activity coupled with substantial decrease in RON which can be enhanced by producing high yield of isomers.