Objective Vertebral aspergillosis is quite rare conditions, often misdiagnosed, that requires long-term antibiotic therapy, and sometimes, surgical treatments. The present investigations were aimed to investigate the epidemiology, clinical-radiological aspects, treatment protocols, and outcomes of Aspergillus-mediated vertebral osteomyelitis. Methods A systematic review of the pertinent English literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was performed. The research was conducted on Cochrane library, MEDLINE, PubMed, and Scopus using as search-terms “Aspergillus,” “vertebral osteomyelitis,” “spondylodiscitis,” “spine infection.” A case of vertebral aspergillosis conservatively managed was also reported. Results Eighty-nine articles were included in our systematic review. Including the reported case, our analysis covered 112 cases of vertebral aspergillosis. Aspergillus fumigatus was isolated in 68 cases (61.2%), Aspergillus flavus in 14 (12.6%), Aspergillus terreus in 4 (3.6%), Aspergillus nidulans in 2 (1.8%). Seventy-three patients (65.7%) completely recovered at the last follow-up evaluation; in 7 patients (6.3%) radiological signs of chronic infection were reported, whereas 32 patients (28.8%) died during the follow-up. Conclusion This systematic review summarized the state of the art on vertebral aspergillosis, retrieving data on clinical features, diagnostic criteria and current limitations, treatment alternatives, and their outcomes.