Although heterosis is widely utilized in crop production, its genetic and molecular basis is still elusive. It is arguably that heterosis arises in crosses between genetically and/or epigenetically distinct individuals. Various genetic models have been proposed to explain heterosis, such as dominance and overdominance hypothesis. With the recent advancements in functional genomics, epigenetics, transcriptomics, proteomics, and metabolomics-related technologies, systems-level approaches have been adopted to understand the molecular basis of heterosis. In this review, we gather a brief account of findings from various studies in order to better understand the genetic and molecular basis of heterosis.