In summary, we report a comprehensive computational analysis of M I M II 4Cl3(bta)6 Kuratowski clusters, which serve as a model for secondary building units of M I M II -MFU-4-type metal-organic frameworks. We showed the scope for tuning the hydrogen binding strength with respect to the substitution of the central atom of the SBU and alteration of the peripheral binding atom. For Cu I M II 4Cl3(bta)6 clusters, we find a linear correlation between the enthalpy and the ionic radius of the central atom, suggesting a continuous tuning potential within the explored range of divalent metal ions. That search also allowed us to identify the Cu I Ca II 4Cl3(bta)6 SBU, which has a hydrogen binding enthalpy within the optimal range and would serve as a non-toxic analogue of the Cu I Cd II 4Cl3(bta)6 SBU. Additionally, the effect of the H2 binding M I atom was investigated. We demonstrated that altering the binding atom from Cu I to Ag I , Ni I , Au I , or Co I can modify the strength of H2-SBU interactions, providing another path for enthalpy adjustment. Using these two degrees of freedom simultaneously, through combinatorial optimization, we identified three novel compounds with binding enthalpies in the desired range for ambient temperature hydrogen storage, specifically Ag I M II 4Cl3(bta)6 (M II = Zn, Mn, Cd). Our estimations of usable capacities also revealed that several new materials surpass the performance of Cu I Cd-MFU-4l SBU, achieving near-theoretical maximum values of up to 62%. Our analysis suggests that certain MFU-4-type frameworks are promising candidates for exhibiting desirable working capacity values for hydrogen storage applications.