A quantitative and qualitative estimation of groundwater resources is a challenge for water management in the world, especially in carbonated and karstified aquifers. Within these aquifers, fault zones exert a significant influence on groundwater hydrodynamics and transport. Improving the management of this type of aquifer involves better assessment of its hydrodynamics properties. Sustainability and management solutions can be estimated through numerical modeling. In this study hydrodynamic parameter of fault zone in karstified carbonate environments are estimated from cross-hole pumping test data. These estimations allow the simulation and forecasting of fault zone flow and transport. For this purpose, a flow and transport model has been set up using MODFLOW6 and MODPATH7 codes. Inverse modeling of hydrodynamic parameters is performed with the PEST++ code suite, with both the Gauss-Levenberg-Marquardt algorithm (GLMA) and the iterative ensemble smoother (IES) which is a recent approach with few applications so far. Simulation, parameter estimation, and forecasts of drawdown and pollutant travel time through the fault zone have been first evaluated on a synthetic fault zone and are eventually applied to a real-world fault zone of interest in karst carbonate environments. A comprehensive comparison and analysis of GLMA and IES results are performed for parameter estimation, parametric and predictive uncertainties, ensuring a thorough assessment of results. The findings reveal satisfactory levels of uncertainty associated with the hydraulic conductivity field and both flow and transport forecasts. This approach demonstrates its ability to estimate the hydrodynamic parameter field with a high level of accuracy within the internal structures of the fault zone. This study constitutes valuable and reproducible insights into the simulation and forecasts of fault zones in karst carbonate aquifers. The findings are a step forward in groundwater flow and transport simulation of fault zones and provide relevant practical help for the management and protection of water resources in these critical areas of interest.