The Yilgarn Craton, Western Australia is endowed with significant gold, nickel‑copper, Cu-Pb-Zn volcanic-hosted massive sulphide (VHMS) and iron ore deposits. Detailed knowledge of the spatial relationships between mineral systems and the crustal framework of the Yilgarn Craton may be powerful tools in the predictive exploration of undiscovered mineral systems. Both Nd and Hf isotopes have the potential to image crustal residence, mantle tapping structures, and juvenile input over both space and time. This study uses a recent compilation of Hf (1236 zircon analyses) and Nd (462 whole rock analyses) isotopes to image the architecture of the crust and compare this to the distribution of gold, nickel‑copper-platinum group elements (Ni-Cu-PGEs), Cu-Pb-Zn VHMS and iron ore deposits. Spatial correlation plots reveal a statistically significant relationship between Nd and Hf isotopic domains and the occurrence of gold, Ni-Cu-PGE, base metals, and iron confirmed by the coefficient of determination (R2) which measures how differences in metal occurrences can be explained by differences in the isotopic signature. Nickel occurrences show the strongest antithetic spatial correlation (R2 = 0.80) with Hf model ages, followed by gold (R2 = 0.58) and base metals (R2 = 0.35), which implies higher metal endowment in areas of more juvenile crust. In contrast, there is a significant positive spatial correlation (R2 = 0.49) between iron ore occurrence and older model ages. Isotopic data can also be plotted as Hf or Nd time-slices, where the strongest spatial correlation between gold, nickel, and base metal occurrence and juvenile input occurs at ca. 2700–2550 Ma. Generally, a model can be proposed where (1) base metals are more prevalent in juvenile crust because of its thinner nature, greater mantle input, high-heat flow, increased water-magma interaction; (2) iron ore is concentrated in regions of old, mature, and stable crust; (3) komatiite-hosted Ni-Cu-PGE systems are focused in juvenile rift zones at the edge of old crustal blocks; and (4) gold is also localised in juvenile crust at craton edges where several factors are localised, including orogenesis, occurrence of previously fertilised crust (i.e. Fe-rich lithologies, sanukitoids), favourable structures (potential inversion of rift structures), and ‘late’ alkaline magmatism. In gold, Ni-Cu-PGE, and base metal mineral systems, the ability of magmas to access higher crustal levels unimpeded appears vital in regional prospectivity and is itself a function of crustal configuration.