Over the last few years, new high-throughput biotechnologies are revolutionizing our ways to utilize human biospecimens for understanding atherosclerotic disease. These recent advances allow deep profiling of individual cells at the genomics, epigenomics, transcriptomics and proteomics levels, or even simultaneous detection of various combinations of ‘Omics’ in the same cell. Additionally, novel methods to integrate data at different levels from tissue sections and dissociated tissues are the emerging trends in large and institutional biobank studies. Growing literature has shown the value of such sequencing and bioinformatic strategies in shedding light on (1) how risk genes, as identified by the Genome-Wide Association Study, contribute to atherogenesis (genotype to phenotype), and (2) how features of atherosclerotic lesions affect patient response in clinical trials (phenotype to the clinical outcome). The hybrid of cutting-edge biotechnologies and bioinformatic approaches helps us maximize biobank resources to accelerate bench-to-bedside research.