OVERALL ABSTRACT Climate change is the greatest global health threat of this century, yet health is not central to research in low and middle income countries that are going to be impacted the most. Adaptation to this threat will create climate- resilient communities and prepare them for climate change extreme events and the long-term impacts. Among the regions across the globe, the Middle East is going to be the epicenter of this impact given a multitude of factors exacerbating the climate change health impacts such as being the most water scarce-region, the region with the highest records of extreme heat, extreme disparity between very poor and very affluent communities, as well as political instability in many of the countries of the region. In that region, Jordan is ranked second in the list of countries with lowest water access and is expected to reach water insecurity by 2030. Within that country, the most water deprived communities live in the Northeast region of Mafraq’s Azraq Basin which is also home to close to 120,000 resettled Syrian refugees that are dependent on the same water resources. Jordan is one of the few politically stable countries in the region, and is aggressively looking for solutions to the water crises in the context of the Water-Food-Energy-Environment nexus and therefore created a high profile governmental committee to develop policies that can address this crises in the short and long-terms. This is why we are proposing the Global Center on Climate Change and Water Energy Food Health Systems (GC3WEFH) to initiate an exploratory phase in Jordan by bringing together scientists with complementary expertise, but diverse perspectives, to address impacts of climate change on water, energy, food, and health systems in the climate-vulnerable communities of the Azraq Basin in Jordan. We will pilot feasible solutions focused on improving health outcomes and in collaboration with the communities that are negatively impacted by climate- related water scarcity. We will involve the communities, local academics, and public officials in capacity building. This network and exploratory phase will become the platform for scale up to other interventions and other countries and regions around the globe. We will demonstrate the utility of engaging vulnerable communities through the systems of Water-Energy-Food-Health. This will be help them explore trade-off decisions to improve adaptation to climate change health impacts, in and this pilot phase, through access to sufficient and good quality water in the Azraq Basin.