BACKGROUND: Sulfamethazine (SMT) has received little attention in the water treatment literature. Yet, SMT is among the non-biodegradable substances increasingly found in aqueous media and affecting both public health and wastewater treatments. For a long time, advanced oxidation processes (AOPs) were studied via pure empirical modeling, although the surface response models resulting from lumped information (TOC, COD, etc.) present limitations regarding extrapolation and optimization. Conversely, detailed first-principles modeling may not be affordable due to the computational burden and the chemical analysis needs. Thus, a balanced approach may be practical in many cases.