Agricultural reuse of treated wastewater (TWW) for irrigation is widely practiced. Its conjunctive use with freshwater is becoming more common to guarantee food security, while the rationale behind and its sustain ability are quite arguable. The objective of this study is to better understand the drivers of the conjunctive use of TWW and groundwater (GW) in Nabeul region, Tunisia, and the potential environmental and health impacts taking into account farmers' practices and attitudes toward reuse. TWW used for irrigation exhibited relatively high salinity and high microbiological load. GW has a very high salinity. TWW and GW showed low concentrations of heavy metals (Al, Cd, Co, Cu, Cr, Mn, Ni, Pb, and Zn). Concentrations of pharmaceutical compounds were between Limits of Quantification and 13 mu g/L. In GW, values were relatively high, especially for caffeine, carbamazepine, ofloxacin, and ketoprofen. Farmers have a low perception of the polluting load of TWW and GW and of their potential long-term impacts on agricultural environment, human health, and agricultural productivity. GW availability has facilitated its conjunctive use with TWW, either to augment water quantity and/or to improve its quality. Despite its low quality, GW timeliness for irrigation was the main driver to guarantee a better yield and quality of produces. Soil microbial community, bacterial biomass, denitrifying potential and carbon oxidation profiles were similar under TWW, GW and their conjunctive use. Though an effect of the sampling period was observed with a high abundance of denitrifying bacteria in the wet season and a low carbon oxidation activity at the end of the dry season. The conjunctive use of TWW and GW is very likely unsustainable from health and environmental perspectives. Balancing farmers' economic profit against the preservation of agricultural activity, linked to cultural and natural heritage, remains one of the challenges for decision-makers and regional stakeholders.