Foot-and-mouth disease (FMD) is one of the most important transboundary animal diseases affecting livestock and wildlife species worldwide. Sustained viral circulation, as evidenced by serological surveys and the recurrence of outbreaks, suggests endemic transmission cycles in some parts of Africa, Asia and the Middle East. This is the result of a complex process in which multiple serotypes, multi-host interactions and numerous socio-epidemiological factors converge to facilitate disease introduction, survival and spread. Spatial and spatio-temporal analyses have been increasingly used to explore the burden of the disease by identifying high-risk areas, analysing temporal trends and exploring the factors that contribute to the outbreaks. We systematically retrieved spatial and spatial-temporal studies on FMD outbreaks to summarize variations on their methodological approaches and identify the epidemiological factors associated with the outbreaks in endemic contexts. Fifty-one studies were included in the final review. A high proportion of papers described and visualized the outbreaks (72.5%) and 49.0% used one or more approaches to study their spatial, temporal and spatio-temporal aggregation. The epidemiological aspects commonly linked to FMD risk are broadly categorizable into themes such as (a) animal demographics and interactions, (b) spatial accessibility, (c) trade, (d) socio-economic and (e) environmental factors. The consistency of these themes across studies underlines the different pathways in which the virus is sustained in endemic areas, with the potential to exploit them to design tailored evidence based-control programmes for the local needs. There was limited data linking the socio-economics of communities and modelled FMD outbreaks, leaving a gap in the current knowledge. A thorough analysis of FMD outbreaks requires a systemic view as multiple epidemiological factors contribute to viral circulation and may improve the accuracy of disease mapping. Future studies should explore the links between socio-economic and epidemiological factors as a foundation for translating the identified opportunities into interventions to improve the outcomes of FMD surveillance and control initiatives in endemic contexts