In this work we leverage simple metal hydride thermodynamic design rules, derived from explainability analysis of compositional ML models, to propose substitution strategies to fine-tune an existing and already promising materials' hydriding thermodynamics for high-pressure compression applications. Upon experimentally measuring PCT curves of the fine-tuned material up to 900 bar at several temperatures, we confirm the ML predicted design rule for desorption enthalpy decrease and demonstrate the material's ability to compress 1 wt% hydrogen from ∼400 bar to ∼875 bar under a temperature swing of 20 to 150 • C. Using a comprehensive system dynamic model for a prototype metal hydride compressor and the experimentally measured PCTs for this new material up to 875 bar (rather than modeled PCTs extrapolated to higher temperatures and pressures), we quantitatively predict efficiency of various multi-stage, high-pressure metal hydride compressor designs. This paves the way to further improve projected efficiencies of materials-based hydrogen compression for various use cases as we continue to further optimize this material.