Anticancer drugs represent emerging contaminants in the water cycle, raising concerns due to their intrinsic biological activity, low concentrations, persistence, and can have potential toxicological effects. Despite growing international concern, few studies have examined their environmental fate in water resources of arid and semi-arid zones, notably in North Africa (Oujda, Morocco). This study investigates the selection rationale, occurrence, and spatial distribution of for five anticancer drugs cyclophosphamide (CP), ifosfamide (IF),5-fluorouracil (5-FU), doxorubicin (DOX) and etoposide (ETO),across aquatic compartments in Oujda, while extending the analysis to the occurrence of anticancer drugs in treated wastewater treatment plant (WWTP) effluents reused for vegetable crop irrigation. In this context, multi-residue methods combining extraction by solid-phase extraction with Oasis HLB cartridges, identification and quantification by high performance liquid chromatography electrospray ultraviolet combined with tandem mass spectrometry. Results revealed the occurrence of major anticancer drug in hospital influents and effluents, wastewater treatment plants effluents, and groundwater at concentrations ranging from 5.866 µg. L-1 to 428.58 µg. L-1. These findings suggest incomplete removal during conventional treatment and a possible contribution of hospital effluents to groundwater contamination. They also point to a potential recirculation route linked to irrigation with treated wastewater, provide initial evidence of anticancer drugs in the water cycle of Oujda, and emphasize the need for improved source control, wastewater treatment, and further research on their environmental behavior.