Over the past years, there has been an increasing concern about the occurrence of antineoplastic drugs in water bodies. The incomplete removal of these pharmaceuticals from wastewaters has been confirmed by several scientists, making it urgent to find a reliable technique or a combination of techniques capable to produce clean and safe water. In this work, the combination of nanofiltration and ozone (O3)-based processes (NF + O3, NF + O3/H2O2 and NF + O3/H2O2/UVA) was studied aiming to produce clean water from wastewater treatment plant (WWTP) secondary effluents to be safely discharged into water bodies, reused in daily practices such as aquaculture activities or for recharging aquifers used as abstraction sources for drinking water production. Nanofiltration was performed in a pilot-scale unit and O3-based processes in a continuous-flow column. The peroxone process (O3/H2O2) was considered the most promising technology to be coupled to nanofiltration, all the target pharmaceuticals being removed at an extent higher than 98% from WWTP secondary effluents, with a DOC reduction up to 92%. The applicability of the clean water stream for recharging aquifers used as abstraction sources for drinking water production was supported by a risk assessment approach, regarding the final concentrations of the target pharmaceuticals. Moreover, the toxicity of the nanofiltration retentate, a polluted stream generated from the nanofiltration system, was greatly decreased after the application of the peroxone process, which evidences the positive impact on the environment of implementing a NF + O3/H2O2 process.