In order to prevent and control the emergence of biosecurity threats such as vector-borne diseases of plants, it is vital to understand drivers of entry, establishment, and spatiotemporal spread, as well as the form, timing, and effectiveness of disease management strategies. An inherent challenge for policy in combatting emerging disease is the uncertainty associated with intervention planning in areas not yet affected, based on models and data from current outbreaks. Following the recent high-profile emergence of the bacterium Xylella fastidiosa in a number of European countries, we review the most pertinent epidemiological uncertainties concerning the dynamics of this bacterium in novel environments. To reduce the considerable ecological and socio-economic impacts of these outbreaks, eco-epidemiological research in a broader range of environmental conditions needs to be conducted and used to inform policy to enhance disease risk assessment, and support successful policy-making decisions. By characterizing infection pathways, we can highlight the uncertainties that surround our knowledge of this disease, drawing attention to how these are amplified when trying to predict and manage outbreaks in currently unaffected locations. To help guide future research and decision-making processes, we invited experts in different fields of plant pathology to identify data to prioritize when developing pest risk assessments. Our analysis revealed that epidemiological uncertainty is mainly driven by the large variety of hosts, vectors, and bacterial strains, leading to a range of different epidemiological characteristics further magnified by novel environmental conditions. These results offer new insights on how eco-epidemiological analyses can enhance understanding of plant disease spread and support management recommendations.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.