This study develops a novel approach for projecting climate trends in the Sahel in relation to shifting livelihood zones and health outcomes. Focusing on Mali, we explore baseline relationships between temperature, precipitation, livelihood, and malnutrition in 407 Demographic and Health Survey (DHS) clusters with a total of 14,238 children, resulting in a thorough spatial analysis of coupled climate-health dynamics. Results suggest links between livelihoods and each measure of malnutrition, as well as a link between climate and stunting. A ‘front-line’ of vulnerability, related to the transition between agricultural and pastoral livelihoods, is identified as an area where mitigation efforts might be usefully targeted. Additionally, climate is projected to 2025 for the Sahel, and demographic trends are introduced to explore how the intersection of climate and demographics may shift the vulnerability ‘front-line’, potentially exposing an additional 6 million people in Mali, up to a million of them children, to heightened risk of malnutrition from climate and livelihood changes. Results indicate that, holding constant morbidity levels, approximately one quarter of a million children will suffer stunting, nearly two hundred thousand will be malnourished, and over one hundred thousand will become anemic in this expanding arid zone by 2025. Climate and health research conducted at finer spatial scales and within shorter projected time lines can identify vulnerability hot spots that are of the highest priority for adaptation interventions; such an analysis can also identify areas with similar characteristics that may be at heightened risk. Such meso-scale coupled human-environment research may facilitate appropriate policy interventions strategically located beyond today’s vulnerability front-line.