Controlling enzootic diseases, which generate a large cumulative burden and are often unregulated, is needed for sustainable farming, competitive agri-food chains, and veterinary public health. We discuss the benefits and challenges of mechanistic epidemiological modelling for livestock enzootics, with particular emphasis on the need for interdisciplinary approaches. We focus on issues arising when modelling pathogen spread at various scales (from farm to the region) to better assess disease control and propose targeted options. We discuss in particular the inclusion of farmers’ strategic decision-making, the integration of within-host scale to refine intervention targeting, and the need to ground models on data.