Multiple System Atrophy (MSA) is a rare, progressive neurodegenerative disorder characterized by a combination of autonomic dysfunction, parkinsonism, and cerebellar ataxia. Diagnostic criteria for MSA have evolved significantly, with recent updates incorporating advanced imaging techniques to enhance early and accurate detection. Pathologically, MSA is defined by the presence of α-synuclein-positive glial cytoplasmic inclusions and is increasingly associated with neuroinflammation, dysregulated iron homeostasis, and demyelination. Management of MSA remains primarily symptomatic, with treatment strategies tailored to address both motor and non-motor symptoms. The two main subtypes—MSA with predominant parkinsonism (MSA-P) and MSA with cerebellar features (MSA-C)—present distinct clinical profiles, each requiring nuanced diagnostic and therapeutic approaches. Recent advances in understanding MSA pathophysiology have driven the development of targeted treatments. These include molecular therapies aimed at reducing α-synuclein aggregation and immunotherapies directed against α-synuclein, though their clinical efficacy is still under investigation. Additionally, approaches targeting neuroinflammation and promoting neuroprotection represent promising areas of research. Despite these developments, current treatment remains largely supportive, focused on alleviating symptoms rather than halting disease progression. The underlying cause of MSA continues to be poorly understood. To improve early diagnosis, therapeutic innovation, and patient outcomes, further refinement of diagnostic criteria, broader inclusion in clinical trials, and the collection of long-term clinical data are urgently needed. This review article consolidates current knowledge on MSA, highlighting recent advancements in diagnosis, pathophysiology, and emerging therapeutic strategies to guide future research and clinical practice.