The study aim was to assess the intrinsic vulnerability of the middle Valseriana (northern Italy) through a methodology that could fully consider the peculiar characteristics of the Pre-Alps region. After applying classical methods for karst environments (COP and EPIK), the integrative COPA+K method was developed for the Nossana (dominant drainage system) and Ponte del Costone (dispersive circulation system) spring catchments. The COPA+K approach exploits the potential of the COP method with the addition of two factors: the influence of the main discontinuities on the water system according to their distance from the spring (A factor), and the development of the karst network (K factor). The COP and COPA+K maps were validated based on the characteristic correlation, for the study area, between the values of δ18O and the elevation of recharge areas. Compared to COP, the COPA+K results appeared more stringent in the identification of areas characterized by high vulnerability, which passed from 35.6% to 23.6% of the entire study area. COPA+K also made possible to better differentiate the behavior of the two catchments. In terms of high susceptible areas, their percentage difference increased by 12.3%, correctly emphasizing the greater susceptibility of the Nossana drainage system in comparison with the Ponte del Costone dispersive one. For the COPA+K map, in the Nossana catchment, the δ18O values indicated a good agreement between the mean elevation of high vulnerable and water recharge areas (± 106 m). For Ponte del Costone, the isotopic data indicated a possible mixing with the waters of the Serio River.