<p>Systemic lupus erythematosus (SLE) is an autoimmune disease that significantly increases the risk of cardiovascular diseases, particularly atherosclerosis (AS). Understanding the shared pathogenic mechanisms underlying SLE and AS is crucial for developing effective therapeutic strategies. Macrophages, as pivotal immune cells, play a critical role in the initiation and progression of atherosclerotic plaques within the context of SLE. This review delves into the molecular and cellular mechanisms governing macrophage activation and differentiation in response to SLE-related inflammatory mediators, highlighting their roles in lipid metabolism, plaque stability, and immune regulation. Additionally, we discussed the current treatment modalities for SLE and their impact on macrophage functionality, exploring these effects for atherosclerotic progression. By elucidating the intricate relationship between macrophages, SLE pathophysiology, and AS progression, this review underscores the need for a multidisciplinary approach in managing SLE and its cardiovascular complications, aiming to improve patient survival and quality of life through tailored therapeutic interventions addressing both autoimmune and cardiovascular pathologies.</p>