Porphyry Cu deposits (PCDs) are major global exploration targets for Cu, Mo, and Au, and mainly formed in accretionary orogens. This study integrates the whole-rock geochemical and Nd isotopic mapping based on ca. 5000 intermediate to felsic magmatic rocks to characterize the crustal structure and metallogeny of PCDs in the Central Asian Orogenic Belt (CAOB), the world’s largest Phanerozoic accretionary orogen. The Nd isotopic maps image clearly the extent of cratons, microcontinents, and juvenile crustal blocks, with the PCDs intimately associated with juvenile crust that is consistent with the conclusions drawn by study in other orogens such as Himalayan–Tibetan. More importantly, PCDs are mainly distributed in the juvenile crust’s margin adjacent to cratons or microcontinents, indicating that the external magmatic arcs are favorable sites for PCDs. The ore-forming intrusions of Cu-Au deposits are isotopically more depleted than those of Cu-Mo deposits, implying more input of mantle or juvenile crust materials into magmatic sources of Cu-Au deposits. Crustal thickness proxy mapping shows that Cu-Au deposits formed in thinner crust than Cu-Mo deposits, which could be used to target favorable sites for mineral exploration. The crustal thickness proxy and εNd(t) define a negative linear relationship, which quantifies the contributions of juvenile materials to PCDs in response to the changing crustal thickness, from which a newly proposed crustal maturity index was derived to distinguish the Cu-Au and Cu-Mo PCDs. The structure of the crust plays an important role in localizing PCDs; therefore, the integrated mapping of Nd isotopes and crustal thickness proxy could provide mappable exploration targets of PCDs at the orogen scale.