The cost-effectiveness of adopting agri-environmental measures (AEMs) in Europe, which combine agricultural productions with reduced N losses, is debated due to poorly targeted site-specific funding that is allocated regardless of local variability. An integrated DAYCENT model-GIS platform was developed combining pedo-climatic and agricultural systems information. The aim was to evaluate best strategies to improve N fluxes of agro-ecosystems within a perspective of sustainable intensification. Indicators of agronomic efficiency and environmental quality were considered. The results showed that agronomic benefits were observed with a continuous soil cover (conservation agriculture and cover crops), which enhanced nitrogen use efficiency (+17%) and crop yields (+34%), although in some cases these might be overestimated due to modelling limitations. An overall environmental improvement was found with continuous soil cover and long-term change from mineral to organic inputs (NLeach < 10> 45 Mg ha−1), which were effective in the sandy soils of western and eastern Veneto with low SOM, improving the soil-water balance and nutrients availability over time. Results suggest that AEM subsidies should be allocated at a site-specific level that includes pedo-climatic variability, following a result-oriented approach.