Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease and demands a comprehensive, multidisciplinary management approach. Early detection of internal organ involvement is crucial, and a wide array of investigations—from serological test to imaging modalities—guide towards diagnosis and prognosis. Management strategies are tailored according to the extent and severity of cutaneous and systemic involvement. This chapter outlines a structured yet adaptable approach to managing SSc, integrating conventional and novel treatments to improve patient outcomes.