Atherosclerosis remains a major contributor to cardiovascular morbidity and mortality, even with widespread use of lipid-lowering, antihypertensive, and anti-inflammatory therapies. The persistent residual risk and endothelial dysfunction highlight the need for targeted, mechanistically driven interventions. Among emerging regulators, microRNAs (miRNAs) offer precise control over gene networks implicated in atherogenesis. This review focuses on two well-characterized miRNAs with complementary roles: miR-33a/b, which impairs cholesterol efflux by targeting ABCA1 and ABCG1, and miR-92a, which disrupts endothelial homeostasis through suppression of KLF2, KLF4, and endothelial nitric oxide synthase (eNOS). We summarize their roles in key signaling pathways, including insulin and nitric oxide signaling, and examine recent advances in antisense oligonucleotide-based therapeutics and nanoparticle-mediated delivery. Together, these miRNAs represent promising precision targets for restoring lipid balance and vascular integrity, with early clinical trials supporting the translational potential of miRNA-based interventions for cardiovascular disease.