Atherosclerosis is a chronic disease characterized by lipid accumulation and inflammation in the intimal layer of arteries, leading to myocardial infarction and stroke. Recent studies have identified triggering receptor expressed on myeloid cells 2 (TREM2) as a lipid-sensing receptor that is highly expressed in macrophage foam cells in both experimental and human atherosclerosis. However, the role of TREM2 in atherosclerosis remains unclear. This study demonstrates that hematopoietic or global TREM2 deficiency increases necrotic core formation in early atherosclerosis, while TREM2 agonism decreases it. TREM2 is essential for the efferocytosis capacities of macrophages and the survival of lipid-laden macrophages, indicating its crucial role in maintaining the balance between foam cell death and clearance of dead cells in atherosclerotic lesions. Single-cell RNA sequencing revealed that TREM2 expression is enriched in lipid-associated/foamy macrophages and is associated with reduced expression of genes involved in lipid metabolism and pro-inflammatory responses. In vitro experiments showed that TREM2 modulates oxLDL uptake by macrophages and promotes macrophage foam cell survival. Additionally, TREM2-deficient macrophages exhibit impaired efferocytosis and altered gene expression responses to efferocytosis. These findings suggest that TREM2 limits atherosclerotic plaque necrosis by enhancing oxLDL uptake, macrophage foam cell survival, and efferocytosis. The study also highlights the potential of TREM2 as a therapeutic target in cardiometabolic diseases.Atherosclerosis is a chronic disease characterized by lipid accumulation and inflammation in the intimal layer of arteries, leading to myocardial infarction and stroke. Recent studies have identified triggering receptor expressed on myeloid cells 2 (TREM2) as a lipid-sensing receptor that is highly expressed in macrophage foam cells in both experimental and human atherosclerosis. However, the role of TREM2 in atherosclerosis remains unclear. This study demonstrates that hematopoietic or global TREM2 deficiency increases necrotic core formation in early atherosclerosis, while TREM2 agonism decreases it. TREM2 is essential for the efferocytosis capacities of macrophages and the survival of lipid-laden macrophages, indicating its crucial role in maintaining the balance between foam cell death and clearance of dead cells in atherosclerotic lesions. Single-cell RNA sequencing revealed that TREM2 expression is enriched in lipid-associated/foamy macrophages and is associated with reduced expression of genes involved in lipid metabolism and pro-inflammatory responses. In vitro experiments showed that TREM2 modulates oxLDL uptake by macrophages and promotes macrophage foam cell survival. Additionally, TREM2-deficient macrophages exhibit impaired efferocytosis and altered gene expression responses to efferocytosis. These findings suggest that TREM2 limits atherosclerotic plaque necrosis by enhancing oxLDL uptake, macrophage foam cell survival, and efferocytosis. The study also highlights the potential of TREM2 as a therapeutic target in cardiometabolic diseases.