Integrative genomics studies have greatly advanced our understanding of cardiovascular pathophysiology over the last decade. Here, we highlight the strengths and challenges of this cutting-edge approach and provide examples where novel insights have arisen through the integration of multi-level genomic information and cardiac physiology. Going forward, the integration of comprehensive next-generation sequencing data sets with quantitative phenotypes at the molecular, cellular, and whole-heart level using advanced modelling approaches provides an unprecedented opportunity for cardiovascular science.