Wastewater effluents are a continuous source of pharmaceuticals in water bodies, which pose a serious environmental threat to aquatic ecosystems. This work provides a comprehensive technical, environmental and cost assessments of different advanced quaternary treatments for wastewater effluents, with special focus on novel Non-Thermal Plasma technology. For this porpouse Non-Thermal Plasma, Sand Filtration + Ozonation, Ultrafiltration, Ultrafiltration + Nanofiltration and Ultrafiltration + Reverse Osmosis technologies were compared with UV disinfection-based technology. This work applies the Life Cycle Analysis tool for the impact environmental assessment using both ReciPE 2016(H) method and, for a more detailed analysis of the contribution of pharmaceuticals to freshwater ecotoxicity category of impact, the USETOX method, which was integrated with 7 new characterisation factors. The results obtained showed overall removal efficiency of pharmaceuticals always higher than 80%, with performances in descending order of Ultrafiltration + Reverse Osmosis > Sand Filtration + Ozonation > Ultrafiltration + Nanofiltration > Non-Thermal Plasma, being Sand Filtration + Ultraviolet disinfection and standalone Ultrafiltration comparatively not suitable for pharmaceuticals removal. Regarding the target pharmaceuticals proposed on the EU Directive 271/91 revision, the Non-Thermal Plasma perform better towards venlafaxine than Sand Filtration + Ozonation, and towards diclofenac and carbamazepine than Ultrafiltration + Nanofiltration. Ultrafiltration + Nanofiltration and Non-Thermal Plasma showed better environmental performance than Sand Filtration + Ozonation and Ultrafiltration + Reverse Osmosis in 7 out of 18 categories of impact (ReciPe method), with Ultrafiltration + Nanofiltration being more advantageous than Non-Thermal Plasma in human and ecotoxicity-related categories of impact, and Non-Thermal Plasma more advantageous in Global Warming, Fossil Resource Scarcity, and Fine Particulate Matter Formation. Regrading Freshwater Ecotoxicity (USEtox method), the quaternary treatment configuration and its energy demand affect the Freshwater final value of impact more than the presence of pharmaceuticals. Under the conditions tested, the Non-Thermal Plasma provided the lower OPEX (0.24 € m−3) than other tested technologies, showing an interesting compromise between pharmaceuticals removal efficiency, environmental impacts, and economic operational cost.