The occurrence of antibiotics in urban wastewater treatment plants (UWTPs) may result in the development of antibiotic resistance and subsequently in the release of multidrug resistant bacteria (MDR) and genes into the effluent. Conventional disinfection processes are only partially effective in controlling ARB spread, so advanced oxidation processes (AOPs) have been investigated as alternative option in this work. In particular, the aim of this work was to comparatively assess the efficiency of solar disinfection and solar driven AOPs (namely H2O2/sunlight, TiO2/sunlight, H2O2/TiO2/sunlight, natural photo-Fenton) for the inactivation of a multidrug (namely ampicillin, ciprofloxacin and tetracycline) resistant E. coli strain isolated from the effluent of the biological process of an UWTP. Different concentrations of H2O2 (0.588–1.470–2.205 mM), TiO2 (50–100 mg L−1), H2O2/TiO2 (0.147 mM/50 mg L−1, 0.588 mM/100 mg L−1) and Fe2+/H2O2 (0.090/0.294, 0.179/0.588, 0.358/1.176 mM) were evaluated at pilot-scale (in compound parabolic collector reactor) in real biologically treated wastewater. All investigated processes resulted in a complete inactivation (5-log decrease) of bacteria until detection limit, but the best disinfection efficiency in terms of treatment time (20 min to reach the detection limit) and required energy (0.98 kJ L−1) was observed for photo-Fenton at pH 4 (Fe2+/H2O2:0.090/0.294 mM). Antimicrobial susceptibility was tested by Kirby-Bauer disk diffusion method. Ampicillin and ciprofloxacin (to which the selected strain is resistant), cefuroxime and nitrofurantoin were chosen as tested antibiotics. None of the investigated processes affected antibiotic resistance of survived colonies.