Background: The complicated inflammatory illness known as systemic lupus erythematosus (SLE) has a chronic relapsing-remitting history and a wide range of clinical presentations, from very minor symptoms to potentially fatal ones. Several variables, including genetic predispositions, environmental influences, and immunological dysregulation, contribute to the complex pathophysiology of SLE. Immune modulation and inflammatory control in SLE are greatly impacted by the ITGAM gene, which encodes the CD11b protein. This gene is critical for leukocyte adhesion, motility, and phagocytosis. This narrative review seeks to investigate the function of ITGAM and the CD11b protein in the development of systemic lupus erythematosus (SLE), with a particular emphasis on the ways in which variations of this protein cause immunological dysregulation and its consequences, including lupus nephritis. In addition, the analysis delves into possible CD11b treatment approaches for inflammation reduction and better patient outcomes. Approach: We combed through the available literature to find research that looked at the link between SLE and ITGAM variants. This review looked at the function of ITGAM in regulating the immune system, phagocytosis, and inflammation. It also looked at new ways to treat SLE, specifically at how CD11b agonists work to control the condition. In summary, SLE pathogenesis is significantly impacted by ITGAM gene variations, which worsen inflammation and hinder immune complex clearance. Potential novel therapy pathways for controlling this complicated autoimmune illness may be found in CD11b-targeted medicines, such as leukadherin-1, which show promise in modifying immune responses and lowering inflammation in SLE, especially in patients with lupus nephritis.