The trans-boundary area between the Europe Union and other countries is highly susceptible to changes in water quality and variations in the potential pollution load that could influence its eco-systems significantly. The Neris (Viliya) River is one of the biggest surface water bodies in Lithuania and Belarus with an ecologically important area protected by international legislation. The study was aimed at evaluating the impacts of integrated pollution on water quality of the Neris River taking into account different storm-water flows and ecological scenarios. For this purpose, qualitative and quantitative statistical evaluation was set up and calculation was done; different integrated pollution loads of the catchment area were estimated. The evaluation considered a decrease in river discharge due to changes in the regional storm-water flow and technological development that should lead to the growing covered surface and a reduction in the untreated storm-water flows. The obtained results indicated that, in the case of storm-water treatment, the total nitrate and phosphate concentrations will decrease, while in the cases of changes in combined suspended solid, the concentration of nutrients will decrease. Thus, a trans-boundary storm-water treatment plant of the Viliya River is required as it should eliminate pollution accumulation and restore its acceptable environmental status. A coordinated international project for the entire catchment of the Neris (Viliya) River based on the specifications and requirements of the EU Water Framework Directive (EU 2000) should be developed and implemented. Subsequently, ecological river-use policies should be established at the international level, which should offer considerable perspectives for the sustainable development of the area.