An optimization methodology is proposed to minimize the catalyst loading cost and the start-of-run temperature of a hydrotreating unit producing ultra-low sulfur diesel by applying a dual-bed catalyst stacking configuration. The methodology involves prior estimation of kinetic parameters for the hydrodesulfurization reaction using experimental data from single-bed evaluations of each catalyst followed by statistical analyses. The variables in the objective function are the order of the two catalyst beds inside the reactor, their volumetric proportions, and the startof-run temperature, along with the restrictions of the target sulfur content (15 ppm) and operating constraints. The results suggest that the difference between the estimated reaction orders of the catalysts influences their optimal sequence and volumetric percentages in a dual-bed configuration to maximize the synergetic effect. The benefits of using an optimized catalyst stacking system include a reduction of 2.6 °C in the start-of-run temperature and an 18.75% cut in the total catalyst cost over a 10-year planning horizon compared to a high-activity catalyst single bed.