The increase in world population and human activities are leading to an increase in water stress in many regions of the planet, coupled with a decrease in the quality of water bodies. Advanced oxidation processes have demonstrated great potential for the reduction of almost any organic pollutant; however, it is necessary to intensify this type of treatment in order to reduce contact times and to reach a greater number of pollutants. The generation of sulfate radicals by activation of peroxymonosulfate (PMS) by divalent iron (Fe2+) and/or titanium dioxide (TiO2) were statistically studied to understand the role of these compounds as activators, using methylene blue as target pollutant because of its ease of handling and analysis. A factorial experimental design was used to study the influence of different variables (PMS, Fe2+, and TiO2) in the presence of UV-A or UV-C. There were relevant differences in the discoloration of methylene blue when analyzing the size of the effects and significance of the experiments, when UV-A or UV-C was used, being faster with UV-C. For instance, total discoloration of methylene blue was reached after 60 min with the system PMS/UV-C, while after 90 min only the 59% of methylene blue disappeared in presence of PMS/UV-A. Both Fe2+ and TiO2 in combination with PMS and UV increased the discoloration effect. So, in the presence of Fe2+, total discoloration of methylene blue was observed after 30 min in presence of UV-A, while this yield was reached in 7.5 min under UV-C. In the case of PMS/TiO2, it required 60 min under UV-A radiation to totally remove methylene blue, and around 15 min with UV-C. Statistically, the three variables were observed to have the main effect in combination with UV. Furthermore, the PMS/Fe2+ system has a significant interaction with UV-A and UV-C radiation, while the interaction of PMS/TiO2 was significant under UV-A, but with a negative effect under UV-C, or in other words the high elimination rates observed are achieved by the oxidation potential of UV-C, and the effect of PMS and TiO2 by itself.