Neuroimaging plays a crucial role in diagnosing multiple system atrophy and monitoring progressive neurodegeneration in this fatal disease. Advanced MRI techniques and post-processing methods have demonstrated significant volume loss and microstructural changes in brain regions well known to be affected by MSA pathology. These observations can be exploited to support the differential diagnosis of MSA distinguishing it from Parkinson's disease and progressive supranuclear palsy with high sensitivity and specificity. Longitudinal studies reveal aggressive neurodegeneration in MSA, with notable atrophy rates in the cerebellum, pons, and putamen. Radiotracer imaging using PET and SPECT has shown characteristic disease-related patterns, aiding in differential diagnosis and tracking disease progression. Future research should focus on early diagnosis, particularly in prodromal stages, and the development of reliable biomarkers for clinical trials. Combining different neuroimaging modalities and machine learning algorithms can enhance diagnostic precision and provide a comprehensive understanding of MSA pathology.