Groundwater in karst aquifers is a valuable resource in Mediterranean region which is particularly threatened by climate change. Climate change induces an increase in evapotranspiration and a decrease in rainfall available for groundwater resource. This impacts directly karst aquifer recharge and thus indirectly karst-river interactions. The study site is a karstic catchment located in the Mediterranean French river basin and known as the “Gorges of the Cèze River”. This site has been studied through interdisciplinary research since 2014 to improve understanding on hydrogeological functioning of this catchment. The river at different points and each of its karstic springs have been equipped with probes and studied by multiple metrics (geochemistry, biology, radioactivity…). As a continuation of these researches, this paper presents an attempt to model the interactions between the whole karstic catchment of the Gorges and the Cèze river and then to predict their evolution regarding to climate change scenarios. The model has been developed using KarstMod software, which consists in an adjustable modelling platform. Firstly, the model has been calibrated on one hydrological cycle and then validated on the following cycle. After that, future climate dataset was simulated by the ALADIN model, according to Intergovernmental Panel on Climate Change (IPCC) Representative Concentration Pathway (RCP) scenario data, including the study area in the above-named model in order to predict karst and river interactions and water production for the period 2030–2100. The results of this work are presented in terms of volume of water produced for three simulations corresponding to three RCP scenarios (2.6, 4.5, and 8.5).