The complete removal of biorecalcitrant xenobiotics, including most notably the pharmaceutical pollutants, by advanced oxidation processes is often difficult to be reached in urban or industrial wastewater because of the high concentration of organic and inorganic scavengers that compete with the xenobiotics for the oxidizing species. This work investigates a coupled treatment train in which wastewater effluents are pretreated with a negatively charged loose nanofiltration (NF) membrane (HydraCoRe70, made up of sulfonated polyethersulfone) to enhance the removal of xenobiotics with the thermal Fenton process. Carbamazepine (CBZ), a drug prescribed mainly for epilepsy treatment, is used here as a model xenobiotic. After optimizing the conditions for separation and degradation, the NF-Fenton approach was applied to both synthetic wastewater and real samples to assess the overall efficiency of CBZ removal. The Fenton degradation of CBZ was drastically enhanced in nanofiltered samples, thanks to the removal by the membrane of nearly all organic matter that would otherwise consume the reactive oxidizing species (e.g., the hydroxyl radical). On the basis of a preliminary treatment cost analysis, it can be concluded that the combined process is potentially applicable to the treatment of several kinds of wastewaters (e.g., industrial ones) to favor the removal of biorecalcitrant contaminants. Key cost savings of NF-Fenton concern the lower amounts of Fenton reagents needed to degrade CBZ and (even more importantly) the decreased levels of acids and bases for pH adjustment before and after the oxidative process because of the lower buffer capacity of the NF permeate compared to feed wastewater, after the removal by the NF of many inorganic ions and most organic carbon.