The achievement of genome-wide association studies (GWAS) has rapidly progressed our understanding of the etiology of coronary artery disease (CAD). It unlocks new strategies to strengthen the stalling of CAD drug development. In this review, we highlighted the recent drawbacks, mainly pointing out those involved in identifying causal genes and interpreting the connections between disease pathology and risk variants. We also benchmark the novel insights into the biological mechanism behind the disease primarily based on outcomes of GWAS. Furthermore, we also shed light on the successful discovery of novel treatment targets by introducing various layers of “omics” data and applying systems genetics strategies. Lastly, we discuss in-depth the significance of precision medicine that is helpful to improve through GWAS analysis in cardiovascular research.