Nowadays, the presence of persistent dissolved pollutants in water has received increasing attention due to their toxic effects on living organisms. Considering the limitations of conventional wastewater treatment processes for the degradation of these compounds, advanced oxidation processes such as electro-Fenton and sono-chemical process, as well as their combination, appear as potentially effective options for the treatment of wastewater contaminated with bio-recalcitrant pollutants. In view of the importance of the development of processes using real effluents, this review aims to provide a comprehensive perspective of sono-electro-Fenton-related processes applied for real wastewater treatment. In the first section, the fundamentals and effectiveness of both homogeneous and heterogeneous electro-Fenton approaches for the treatment of real wastewater are presented. While the second part of this work describes the fundamentals of ultrasound-based processes, the last section focuses on the coupling of the two methods for real wastewater treatment and on the effect of the main operational parameters of the process. On the basis of the information presented, it is suggested that sono-electro-Fenton processes substantially increase the efficiency of the treatment as well as the biodegradability of the treated wastewater. The combined effect results from mass transfer improvement, electrode cleaning and activation, water electrolysis, and the electro-Fenton-induced production of hydroxyl radicals. The information presented in this work is expected to be useful for closing the gap between laboratory-scale assays and the development of novel wastewater technologies.