SUMMARYHeterosis, also known as hybrid vigor, is the phenomenon wherein a progeny exhibits superior traits relative to one or both parents. In terms of crop breeding, this usually refers to the yield advantage of F1 hybrids over both inbred parents. The development of high‐yielding hybrid cultivars across a wider range of crops is key to meeting future food demands. However, conventional hybrid breeding strategies are proving to be exceptionally challenging to apply commercially in many self‐pollinating crops, particularly wheat and barley. Currently in these crops, the relative performance advantage of hybrids over inbred line cultivars does not outweigh the cost of hybrid seed production. Here, we review the genetic basis of heterosis, discuss the challenges in hybrid breeding, and propose a strategy to recruit multiple heterosis‐associated genes to develop lines with improved agronomic characteristics. This strategy leverages modern genetic engineering tools to synthesize supergenes by fusing multiple heterotic alleles across multiple heterosis‐associated loci. We outline a plan to assess the feasibility of this approach to improve line performance using barley (Hordeum vulgare) as the model self‐pollinating crop species, and a few heterosis‐associated genes. The proposed method can be applied to all crops for which heterotic gene combinations can be identified.