We report a case of a 39-year-old woman with resistant hypertension and renal dysfunction. The patient was hospitalized 3 months earlier for dyspnea at the Department of Cardiology, where she was diagnosed with heart failure (left ventricle injection fraction: 25–30%), pulmonary hypertension, chronic kidney disease (serum creatinine: 1.58 mg/dl), and resistant hypertension and discharged with optimal heart failure treatment. At presentation to our clinic, apart from uncontrolled hypertension for more than 10 years and history of pre-eclampsia and fetal loss, the patient had obesity (BMI: 38 kg/m2) and facial fibromas. The first diagnostic steps proposed by the European Society of Hypertension/European Society of Cardiology (ESH/ESC) Guidelines to identify other target-organ damage and causes of secondary hypertension revealed typical proteinuric hypertensive nephropathy, hypertensive retinopathy, and sleep-apnea syndrome. Furthermore, a renal ultrasound showed multiple bilateral renal angiomyolipomas, confirmed by an MRI scan. Following consultation with the Neurology and Dermatology Departments, the diagnosis of tuberous sclerosis complex, based on presence of six major criteria, was confirmed. During the following 10 months, careful adjustments in the patient's antihypertensive treatment, reinforcement of lifestyle interventions, and improved compliance enabled her to reduce her body weight, control blood pressure, improve her heart (left ventricle injection fraction: >40%), and renal injury (creatinine urine clearance: 125 ml/min, urine protein: 178 mg/24 day) and serum triglycerides (153 mg/dl). These improvements enabled the start of everolimus, required for a slight increase in angiomyolipomas’ size (3.46 cm) in the repeated examinations.