Abstract Background Risk communication interventions during epidemics aim to modify risk perceptions to achieve rapid shifts in population health behaviours. Exposure to frequent and often concurrent epidemics may influence how the public and health professionals perceive and respond to epidemic risks. This review aimed to systematically examine the evidence on risk perceptions of epidemic-prone diseases in countries highly vulnerable to epidemics. Methods We conducted a systematic review using PRISMA standards. We included peer-reviewed studies describing or measuring risk perceptions of epidemic-prone diseases among the general adult population or health professionals in 62 countries considered highly vulnerable to epidemics. We searched seven bibliographic databases and applied a four-stage screening and selection process, followed by quality appraisal. We conducted a narrative meta-synthesis and descriptive summary of the evidence, guided by the Social Amplification of Risk Framework. Results Fifty-six studies were eligible for the final review. They were conducted in eighteen countries and addressed thirteen epidemic-prone diseases. Forty-five studies were quantitative, six qualitative and five used mixed methods. Forty-one studies described epidemic risk perceptions in the general public and nineteen among health professionals. Perceived severity of epidemic-prone diseases appeared high across public and health professional populations. However, perceived likelihood of acquiring disease varied from low to moderate to high among the general public, and appeared consistently high amongst health professionals. Other occupational groups with high exposure to specific diseases, such as bushmeat handlers, reported even lower perceived likelihood than the general population. Among health professionals, the safety and effectiveness of the work environment and of the broader health system response influenced perceptions. Among the general population, disease severity, familiarity and controllability of diseases were influential factors. However, the evidence on how epidemic risk perceptions are formed or modified in these populations is limited. Conclusions The evidence affords some insights into patterns of epidemic risk perception and influencing factors, but inadequately explores what underlies perceptions and their variability, particularly among diseases, populations and over time. Approaches to defining and measuring epidemic risk perceptions are relatively underdeveloped. Graphical Abstract