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Safe and timely disposal of high-level nuclear waste is an urgent global priority due to risks associated with prolonged above-ground storage, including geopolitical instability, environmental hazards, and potential contamination. Geological Disposal Facilities (GDFs), which isolate radioactive waste deep underground within stable geological formations, are internationally recognised as the most effective solution. These facilities rely on a multi-barrier approach, combining engineered vaults with natural geological barriers to ensure long-term containment and isolation. In the UK, current site evaluations for a GDF have provisionally identified the Triassic Mercia Mudstone Group (MMG) as a suitable geological barrier. The MMG is considered attractive due to its widespread availability, low permeability, proven effectiveness as hydrocarbon seals, and favourable mechanical properties. However, to fully assess its suitability, it is important to consider the geological complexity. The MMG exhibits significant heterogeneity, with marked vertical and lateral changes in sedimentary facies and lithological composition over short distances. In addition, its diagenetic history, involving burial at depths exceeding those targeted for geological disposal, has resulted in over-compaction and relatively stiff and brittle rock properties. These characteristics may influence fracture behaviour and permeability and therefore warrant detailed characterisation during site assessments. Reliable permeability measurement in these ultra-low permeability mudrocks is challenging yet crucial, as even minor leakage could have severe environmental consequences. This research addresses this critical knowledge gap by developing robust, reproducible laboratory methods specifically tailored to measure permeability in MMG samples obtained from the Gateway 1e borehole. Using highly saline fluids representative of realistic repository conditions, we systematically measure permeability under subsurface pressure conditions and varying ionic strengths, closely simulating in situ geological environments. This approach addresses key methodological gaps in permeability assessment, particularly concerning fluid-rock interactions under realistic salinities. Such targeted experimentation, rarely conducted before, will produce essential reference data and novel empirical correlations, facilitating accurate permeability upscaling and improved numerical modelling for site assessments. By enhancing the accuracy and reliability of permeability measurements in the complex geological context of the MMG, our findings will provide crucial scientific evidence for the UK’s ongoing GDF siting process. This will support informed decisions about geological suitability, engineering feasibility, and long-term safety, while also offering valuable insights and reference methods applicable to similar geological disposal programmes worldwide.