A 2-year-old, spayed female, American shorthair cat presented with acute weight loss, tachypnea, and dyspnea. The cat had grade V holosystolic murmur and systemic hypotension. Echocardiography showed a 9 mm defect in the ventricular septum, left-to-right dominant bi-directional shunt, right ventricular hypertrophy, pulmonary stenosis, pulmonary hypertension, and overriding aorta. The cat was diagnosed with a Tetralogy of Fallot. The cat was treated with furosemide, pimobendan, ramipril, and sildenafil. Treatment reduced pulmonary infiltration, pulmonary vessel enlargement, and main pulmonary artery bulging. However, right-to-left flow increased over time and right ventricular outflow tract velocity was elevated. Currently, the patient has maintained an improved state for 1 year. This case report described a severe inherited feline Tetralogy of Fallot case that was successfully managed for a long time.