Global health threats including epidemics and climate change, know no political borders and require regional collaboration if they are to be dealt with effectively. This paper starts with a review of the COVID-19 outbreak in Israel, Palestine and Jordan, in the context of the regional health systems, demography and politics. We suggest that Israel and Palestine function as one epidemiological unit, due to extensive border crossing of inhabitants and tourists, resulting in cross-border infections and potential for outbreaks' transmission. Indeed, there is a correlation between the numbers of confirmed cases with a 2-3 weeks lag. In contrast, Jordan has the ability to seal its borders and better contain the spread of the virus. We then discuss comparative public health aspects in relation to the management of COVID-19 and long term adaptation to climate change. We suggest that lessons from the current crisis can inform regional adaptation to climate change. There is an urgent need for better health surveillance, data sharing across borders, and more resilient health systems that are prepared and equipped for emergencies. Another essential and currently missing prerequisite is close cooperation within and across countries amidst political conflict, in order to protect the public health of all inhabitants of the region.