The increasing demand for novel inorganic materials with targeted functionality motivates moving beyond the area of traditionally explored near‐equilibrium materials by incorporating metastable phase space into materials design and discovery. It has recently been shown that heterostructural semiconductor alloys can exhibit increased regions of metastable phase space as compared to their isostructural counterparts. This phase space is accessible using non‐equilibrium deposition techniques, providing ample opportunities for the synthesis of novel, metastable, single‐phase alloys. In addition, the composition‐dependent structural transitions in heterostructural systems provide additional degrees of freedom for the tuning of functional properties. This perspective gives insight into the design of heterostructural semiconductor alloys and highlights their potential for future materials discovery. It is shown how combinatorial, non‐equilibrium physical vapor deposition can be used to effectively screen and access previously uncharted metastable phase space in such systems. In addition, it is demonstrated how differences in mixing enthalpies for different structures can be utilized to stabilize new alloy polymorphs with useful properties that cannot be found in either of the alloying endmembers. Finally, it is discussed how this conceptual approach can be used to screen high‐throughput computational databases, potentially revealing numerous materials systems where such novel metastable polymorphs can be discovered.