Conventional wastewater treatment systems have limitations in removing diverse micropollutants present with the complex matrix. As an alternative, advanced oxidation processes such as gamma-irradiation have been proposed. The aim of the study was to get insight into the decomposition of persistent pharmaceuticals (carbamazepine, cetirizine, tramadol) by gamma irradiation in pure water and effluent, and the formation and pathway of transformation products (TPs) identified via suspect/non-target screening using LC-HRMS. For TPs, the environmental risk assessment was also conducted with Quantitative Structure Activity Relationship (QSAR) based estimations. The decomposition effect was estimated with the removal rate and radiation chemical yield (G-value). The results indicated that the removal rate increased as the absorbed dose increased, up to 5 kGy, completely eliminating the target pharmaceuticals (initial nominal concentration: 10 mg/L) in pure water. However, the degradation in effluent was negatively affected by the organic matrix. By employing suspect/non-target screening techniques, a tentative identification of 30 transformation products (TPs) was achieved, providing insights into the degradation pathway. They were mainly formed through hydroxylation reaction by OH⸱. As a result of the QSAR estimation for the hazard of TPs, most of the TPs showed a lower risk than the parent compound. It indicates that the gamma-irradiation can be used as an alternative process to eliminate hardly degradable micropollutants in conventional wastewater treatment plant in a way to mitigate the environmental risk.