This work investigated an innovative alternative to improve municipal wastewater treatment plant effluent (MWWTP effluent) quality aiming at the removal of contaminants of emerging concern (caffeine, carbendazim, and losartan potassium), and antibiotic-resistant bacteria (ARB), as well as disinfection (E. coli). Persulfate was used as an alternative oxidant in the solar photo-Fenton process (solar/Fe/S2O82−) due to its greater stability in the presence of matrix components. The efficiency of solar/Fe/S2O82− at neutral pH using intermittent iron additions is unprecedented in the literature. At first, solar/Fe/S2O82− was performed in a solar simulator (30 W m−2) leading to more than 60% removal of CECs, and the intermittent iron addition strategy was proved effective. Then, solar/Fe/S2O82− and solar/Fe/H2O2 were compared in semi-pilot scale in a raceway pond reactor (RPR) and a cost analysis was performed. Solar/Fe/S2O82− showed higher efficiencies of removal of target CECs (55%), E. coli (3 log units), and ARB (3 to 4 log units) within 1.9 kJ L−1 of accumulated irradiation compared to solar/Fe/H2O2 (CECs, 49%; E. coli, 2 log units; ARB, 1 to 3 log units in 2.5 kJ L−1). None of the treatments generated acute toxicity upon Allivibrio fischeri. Lower total cost was obtained using S2O82− (0.6 € m−3) compared to H2O2 (1.2 € m−3). Therefore, the iron intermittent addition aligned to the use of persulfate is suitable for MWWTP effluent quality improvement at neutral pH.