Malaria is a persistent health risk for most rural communities in tropical wetlands of developing countries, particularly in the advent of climate change. This chapter assesses household access to water resources, livelihood assets, and vulnerability to malaria in the Okavango Delta of north-western Botswana. Data were obtained from a cross-sectional survey of 355 households, key informant interviews, PRA-based focus group discussions (FDGs), interviews with experts in various related fields, PRA workshop participant interviews, and literature review. There was high access to natural capital, and most households engaged in nature-based livelihood activities. Access to resources determined type of livelihood activities that households engaged in. However, there was no association between household exposure and/or susceptibility, and type of livelihood activities pursued by households. Household vulnerability to malaria was higher in remote and rural locations than in urban neighborhoods. Malaria prevention and vulnerability aversion programs need to be coupled with improvements in housing and well-being in the Okavango Delta and similar wetlands.