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Colloidal growth modes reliant on the replication of the crystalline character of a preexisting seed through homoepitaxial or heteroepitaxial depositions have enriched both the architectural diversity and functionality of noble metal nanostructures. Equivalent syntheses, when practiced on seeds formed on a crystalline substrate, must reconcile with the fact that the substrate enters the syntheses as a chemically distinct bulk-scale component that has the potential to impose its own epitaxial influences. Herein, we provide an understanding of the formation of epitaxial interfaces within the context of a hybrid growth mode that sees substrate-based seeds fabricated at high temperatures in the vapor phase on single-crystal oxide substrates and then exposed to a low-temperature liquid-phase synthesis yielding highly faceted nanostructures with a single-crystal character. Using two representative syntheses in which gold nanoplates and silver–platinum core–shell structures are formed, it is shown that the hybrid system behaves unconventionally in terms of epitaxy in that the substrate imposes an epitaxial relationship on the seed but remains relatively inactive as the metal seed imposes an epitaxial relationship on the growing nanostructure. With epitaxy transduced from substrate to seed to nanostructure through what is, in essence, a relay system, all of the nanostructures formed in a given synthesis end up with the same crystallographic orientation relative to the underlying substrate. This work advances the use of substrate-induced epitaxy as a synthetic control in the fabrication of on-chip devices reliant on the collective response of identically aligned nanostructures.