Hydrogeological numerical models are crucial for assessing radioactive waste disposal. State variables are widely used but not quantitatively during model inversion, except for hydraulic head. This study explores incorporating radiogenic Helium-4 (4Herad) as an unconventional state variable in model inversion, addressing parameter solution non-uniqueness. Employing a formal Bayesian approach, two 3D physically-based models are used to infer posterior parameter distributions. Major 4Herad sources include crustal fluxes and in situ production in the Boom Clay. Coupled inference narrows marginal posterior distributions, reducing uncertainty in calibration and prediction of certain parameters. Integrating 4Herad as a state variable improves model reliability and fidelity, particularly in constraining solute transport and refining groundwater flow parameters and derived fluxes. This state-of-the-art study demonstrates the effectiveness of including 4Herad in combination with classical hydraulic head observations, showcasing transformative potential for reducing uncertainties crucial for radioactive waste disposal. It marks the first-ever attempt at harnessing 4Herad quantitative insights into flow and transport parameters following a Bayesian approach at a catchment scale, setting a precedent for future research. The study strongly advocates for the continued utilization of 4Herad in hydrogeological modeling, emphasizing its relevance for safety studies.