Background: This case report presents a 30-year-old female patient with a history of systemic lupus erythematosus (SLE) leading to lupus nephropathy, currently managed with peritoneal dialysis and immunosuppressive therapy. Case Description: The patient experienced worsening dyspnea and angina, prompting medical attention. Echocardiography revealed significant mitral and tricuspid regurgitation, with subsequent development of resting angina associated with autonomic nervous system dysfunction. Rheumatological assessment initially discounted active lupus. Cardiac catheterization confirmed intravascular coronary artery disease, including coronary dissection of intermediate and circumflex branches with associated coronary ectasia. Treatment and Outcome: Cardiothoracic surgery considered tricuspid plasty, mitral valve replacement, and coronary artery bypass grafting following dissection of multiple coronary branches. Spontaneous coronary dissection, more common in women, manifested as unstable angina, with a rare incidence of 0.43% associated with SLE: extra-renal vasculitis, a rare complication of lupus nephropathy, further complicated management. Conclusion: Individualized treatment strategies are essential, considering the extent of vessel involvement and hemodynamic status in patients with SLE-related coronary artery disease. Early recognition and multidisciplinary management are critical in optimizing outcomes for such complex cases.