We introduce LuKARS 3.0, an optimized and flexible version of the LuKARS semi-distributed karst simulation model, designed for improved computational efficiency in discharge and reactive transport simulations. Code optimization and a flexible model structure enabled extensive sensitivity and uncertainty analyses. We demonstrate it with three applications. First, we tested the reduction in runtime, achieving a 420-fold decrease. Second, we implemented the Morris sensitivity analysis, producing results comparable to the active subspace method. Third, we performed combined structural and parametric uncertainty analyses revealing that increasing hydrotopes does not necessarily enhance model performance. Additionally, we couple LuKARS 3.0 with IPhreeqc to implement a solute transport model based on complete mixing. Results show that discharge performance metrics alone may not fully capture solute transport dynamics, highlighting the need for a multi-objective approach. These advancements make LuKARS 3.0 a powerful tool for large-scale karst hydrology studies, with future applications aimed at integrating chemical reactions and enhancing uncertainty analyses for water resource management.