A comprehensive cellular atlas analyzed over one million cells from human atherosclerotic arteries, identifying specific transcription factors including PRRX1, BNC2, and ELK3 that regulate disease-relevant cellular programs in smooth muscle and endothelial cells. The research mapped cardiovascular genome-wide association study signals to precise cell types and uncovered regulatory mechanisms governing harmful cellular transitions like osteogenic smooth muscle cells and endothelial-to-mesenchymal transitions. This granular cellular mapping represents a significant advance in understanding atherosclerosis at the molecular level. The identification of specific transcription factors provides concrete targets for therapeutic intervention, moving beyond broad anti-inflammatory approaches to precision targeting of disease-driving cellular programs. The ability to link genetic risk variants to specific cell types and regulatory networks could transform how we assess cardiovascular risk and develop personalized treatments. However, this work examines diseased tissue rather than tracking disease progression, limiting insights into causation versus consequence. As a preprint awaiting peer review, these findings require validation before clinical application. The atlas methodology could prove paradigm-shifting for cardiovascular research, offering unprecedented resolution of disease mechanisms.