Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) can manifest with a severe vasculopathic phenotype. We report a case of anti-MDA5 DM in a woman in her early 30s complicated by refractory cutaneous ulcers and pulmonary arterial hypertension (PAH). Despite the escalation of immunosuppressive therapy with glucocorticoids, tacrolimus, intravenous immunoglobulin, and cyclophosphamide, the cutaneous ulcers remained refractory. A progressive decline in diffusing capacity of the lung for carbon monoxide raised suspicion of PAH, which was subsequently confirmed by right heart catheterization. Consequently, combination therapy with mycophenolate mofetil (MMF) and rituximab (RTX) was initiated alongside bosentan. This regimen resulted in the prompt resolution of ulcers and improvement of PAH. Bosentan was discontinued, and azathioprine was initiated to maintain remission, allowing for a successful pregnancy and delivery of a healthy infant. This case suggests a potential role for an MMF- and RTX-containing combination regimen in refractory cutaneous ulcers and PAH associated with anti-MDA5 DM.