OBJECTIVES: Complex challenges such as political instability, climate change and population displacement are increasing threats to national disease control, elimination and eradication programmes. The objective of this study was to determine the burden and risk of conflict-related and climate-related internal displacements and the need for strategies for countries endemic with neglected tropical diseases (NTDs). DESIGN, SETTING AND OUTCOME MEASURES: A cross-sectional ecological study was conducted including countries that are endemic with at least one of five NTDs requiring preventive chemotherapy in the African region. For each country, the number of NTDs, population size and the number and rate per 100 000 of conflict-related and natural disaster-related internal displacements reported in 2021 were classified into high and low categories and used in unison to stratify and map the burden and risk. RESULTS: This analysis identified 45 NTD-endemic countries; 8 countries were co-endemic with 4 or 5 diseases and had populations classified as 'high' totalling >619 million people. We found 32 endemic countries had data on internal displacements related to conflict and disasters (n=16), disasters only (n=15) or conflict only (n=1). Six countries had both high conflict-related and disaster-related internal displacement numbers totalling >10.8 million people, and five countries had combined high conflict-related and disaster-related internal displacement rates, ranging from 770.8 to 7088.1 per 100 000 population. Weather-related hazards were the main cause of natural disaster-related displacements, predominately floods. CONCLUSIONS: This paper presents a risk stratified approach to better understand the potential impact of these complex intersecting challenges. We advocate for a 'call to action' to encourage national and international stakeholders to further develop, implement and evaluate strategies to better assess NTD endemicity, and deliver interventions, in areas at risk of, or experiencing, conflict and climate disasters, in order to help meet the national targets.