The endemic circulation of bovine brucellosis in cattle herds has a markedly negative impact on economy, due to decreased fertility, increased abortion rates, reduced milk and meat production. It also poses a direct threat to human health. In Italy, despite the long lasting efforts and the considerable economic investment, complete eradication of this disease still eludes the southern regions, as opposed to the northern regions that are disease-free. Here we introduced a novel quantitative network-based approach able to fully exploit the highly resolved databases of cattle trade movements and outbreak reports to yield estimates of the vulnerability of a cattle market to brucellosis. Tested on the affected regions, the introduced vulnerability indicator was shown to be accurate in predicting the number of bovine brucellosis outbreaks (Spearman r= 0.82, p= 0.04), thus confirming the suitability of our tool for epidemic risk assessment. We evaluated the dependence of regional vulnerability to brucellosis on a set of factors including premises spatial distribution, trading patterns, farming practices, herd market value, compliance to outbreak regulations, and exploring different epidemiological conditions. Animal trade movements were identified as a major route for brucellosis spread between farms (r=0.85, p{ extbackslash}textless10-5 between vulnerability and number of inbound movements), with an additional potential risk attributed to the use of shared pastures (r=0.4, p=0.04). By comparing the vulnerability of disease-free regions in the north to affected regions in the south, we found that more intense trade and higher market value of the cattle sector in the north (r=0.56, p=0.01) likely inducing more efficient biosafety measures, together with poor compliance to trade restrictions following outbreaks in the south were key factors explaining the diverse success in eradicating brucellosis. Our modeling scheme is both synthetic and effective in gauging regional vulnerability to brucellosis persistence. Its general formulation makes it adaptable to other diseases and host species, providing a useful tool for veterinary epidemiology and policy assessment.