Background <p>Malaria remains a pressing public health challenge in sub-Saharan Africa, particularly in West Africa. Benin, a West African country, is currently confronted with the significant challenge of malaria infection, a public health crisis that can be attributed to the impact of climate change.</p> Methods <p>This study aims to comprehensively assess vulnerability to malaria in the northern region of Benin. The assessment employed a range of exposure, susceptibility, and lack of resilience indicators to quantify vulnerability. Principal component analysis (PCA) is applied to construct a Malaria Vulnerability Index (VI) for geographic visualization. Correlations between VI and various indicators are examined to identify significant contributors to vulnerability through Pearson correlation.</p> Results <p>The levels of vulnerability to malaria vary within the study area. Materi, Cobli, Boukoumbe, and Perere districts exhibit the highest vulnerability. Contrary, districts like Kerou, Pehonco, Nikki, Ouake, Parakou, Kouande, Copargo, Djougou, and Tchaourou have lower vulnerability owing to factors such as a lower prevalence of household members, and higher use rates of insecticide-treated net (ITN). In addition to some indicators of resilience such as owning mobile phones, livestock, and using natural gas for cooking.</p> Conclusion <p>These findings are useful tools for policymakers, healthcare practitioners, and organisations dedicated to malaria prevention and control, emphasising the necessity of targeted methods to reduce vulnerability and increase resilience to malaria in northern Benin.</p>