Purpose of Review <p>This review examines anti-atherogenic mechanisms and the crucial role of efferocytosis in promoting inflammation resolution, with a focus on innovative, resolution-based therapeutic strategies that aim to restore vascular homeostasis and mitigate atherosclerosis progression.</p> Recent Findings <p>Atherosclerosis, a chronic inflammatory condition, is exacerbated by impaired efferocytosis, which contributes to plaque instability and the expansion of the necrotic core. Advanced molecular and cellular profiling has revealed diverse macrophage populations and their metabolic adaptations during efferocytosis, which drive the production of resolving mediators essential for tissue repair. Dysregulated signaling and metabolic pathways disrupt the efficient clearance of apoptotic cells, exacerbating inflammation. Molecular regulators, such as microRNAs, further impact efferocytosis, governing cardiovascular outcomes. Resolution-based therapies, including specialized pro-resolving mediators, peptides, and metabolites, enhance the successive clearance of apoptotic cells while maintaining host immune function, offering advantages over traditional immunosuppressive approaches. Additionally, vaccines targeting disease-specific antigens show promise in eliciting protective immune responses that can help ameliorate atherosclerosis.</p> Summary <p>Efferocytosis is a key regulator of inflammation resolution in atherosclerosis, linking macrophage metabolism to plaque stability. Its disruption drives disease progression, but emerging therapies targeting resolution pathways, metabolic reprogramming, and immune modulation hold the potential for effective interventions. Advances in profiling technologies and targeted delivery systems will address translational challenges, paving the way for precision medicine in treating atherosclerotic cardiovascular disease.</p>