In the study of heart disease, heart organoids derived from induced pluripotent stem cells (iPSCs) are game-changers. These 3D mini-heart models closely mimic the complexity of the human heart, making them invaluable for research. When combined with Perturb-seq, a technique that merges CRISPR gene editing with single-cell RNA sequencing, we can map the transcriptional effects of genetic perturbations at single-cell resolution. Combining CRISPR-based genetic screening with information-rich, single-cell RNA-sequencing phenotypes allows for an exceptionally detailed understanding of disease mechanisms and revolutionize the way to identify druggable targets.