Congenital heart disease (CHD) is the leading cause of mortality associated with birth defects.Whole-genome sequencing and whole-exome sequencing technologies have resulted in major advancements in our understanding of the genetics of CHD, and cell and animal models have emerged as reliable options for investigating the specific genetic mechanisms and factors underlying CHD. Human induced pluripotent stem cells (iPSCs) offer a novel approach for studying CHD by generating patient-specific iPSC-derived cardiomyocytes for related research. Inaddition, CRISPR-Cas9 gene editing tools enable the introduction or correction of variant genes in iPSCs, thus facilitating a more comprehensive exploration of variant pathogenicity and the molecular basis of CHD. This review considers the progress in understanding the genetic basis of CHD using genome sequencing, and explores how gene editing techniques and patient iPSCs contribute to this progress. We highlight the significance of combining these two approaches for disease research, providing valuable insights for clinical investigations on the mechanisms responsible for CHD.