Colloidal syntheses have unequivocally demonstrated seed design as a decisive factor in determining the growth pathway along which an emerging nanostructure follows. With the seed size, shape, composition, and internal defect structure all proving crucial, there has been a concerted effort to manipulate the seed formation process. Seed preparation techniques reliant on oxidative etching, capping agents, centrifugation, and kinetically and thermodynamically controlled regimes are now routinely used. Our group has devised a synthetic strategy in which seed-mediated colloidal syntheses are practiced on nanostructures that are immobilized on the substrate surface. While numerous seed-mediated colloidal growth modes have been adapted to the substrate platform, much of the prior art pertaining to seed formation proves unadaptable or is drastically altered by the substrate surface. Instead, seeds are formed in periodic arrays using a vapor-phase directed assembly technique that is most closely related to solid-state dewetting. Within the scope of this strategy lies numerous opportunities to place new controls on the seed formation process that are reliant on such factors as substrate-imposed epitaxy and the engineering of defects through substrate-imposed strain. Moreover, these seeds can then be used to form unique templates suitable for heterogeneous depositions or galvanic replacement reactions. Here, we will describe the techniques used to generate seeds, demonstrate their utility in forming substrate-based noble metal nanostructures, and provide an understanding of the opportunities and challenges that lie ahead.