The frequent detection and occurrence of pharmaceuticals in surface waters pose a significant challenge to achieving good status for waterbodies under the Water Framework Directive. Active pharmaceutical ingredients (APIs) are increasingly recognised as contaminants of emerging concern (CECs) due to their biological activity and persistence in aquatic ecosystems. Although previous studies have shown the presence of pharmaceuticals in Irish rivers, there is still the need for a greater focus on monitoring efforts to better understand the extent and potential environmental impact posed by APIs. Monitoring in the rivers Nore, Suir, Liffey, and Analee between 2020 and 2021 yielded crucial occurrence data that revealed the presence of 15 pharmaceuticals, with seven detected in all samples with concentration ranging from <LOD to 290.25 ng/L. Additionally, the observed increase in O-desmethyl venlafaxine concentrations following the easing of level 5 restrictions indicated that COVID-19 lockdown measures were a contributing factor to its presence in Irish rivers, aligning with studies from the UK and Italy. By integrating risk quotient analysis and leveraging effect-based biomonitoring tools, this study identified the antibiotic sulfamethoxazole and the antidepressant venlafaxine, along with its metabolite (O-desmethyl venlafaxine), as pharmaceuticals posing a high risk to Irish river ecosystems, in particular the Liffey at Lucan. A thorough examination of passive and grab sampling passive techniques demonstrated the effectiveness of passive sampling in monitoring pharmaceuticals for point source identification. Source identification was achieved through the deployment of several passive samplers at strategic locations (upstream, discharge site and downstream), showing elevated concentrations of several pharmaceuticals at the discharge site. Moreover, this study demonstrated that employing passive samplers for pharmaceutical monitoring in remote locations can help to identify the presence of pharmaceuticals that could remain undetected through traditional grab sampling methods. This project provided an in-depth investigation of pharmaceutical presence, occurrence and effect within Irish surface water environments, showing the importance of monitoring pharmaceuticals in surface waters and enhancing our understanding of water quality.