The results of long-term groundwater monitoring in the Bileća reservoir adjacent (eastern Herzegovina, Bosnia and Herzegovina) indicate that there is a good hydraulic connection between the reservoir and the karst aquifer located in the right bank of the reservoir. In remote parts of the right-bank karst aquifer, due to complex lithostratigraphic characteristics and a tectonic structure, the influence of the reservoir is very variable and has been insufficiently studied up until now. This paper presents the analysis and synthesis of new, relevant hydrogeological data, as a basis for the creation of a 3D spatial model, i.e., the analysis of the karst system’s behaviour, both under regular and artificial hydrological conditions of surface reservoir construction and its continuous use (filling and emptying). The interactive connection of the model and complex surface and groundwater time series monitoring data of this system is presented through the analysis of its hydrodynamic characteristics, which completes the spatial model of the karst regime caused by low and high groundwater levels and low and high reservoir water levels. The integration of all the data into one model and further multiparametric analyses revealed the different types of hydrodynamic conditions prevailing in the karst aquifer with regard to the influence of the high or low waters of the reservoir.