The present paper aims to elucidate impacts of climate change on the availability and security of water and energy in the Middle East and North Africa region (MENA region; including the Eastern Mediterranean) in the context of the water–energy nexus. It largely builds on existing knowledge and understanding and aims to present a review of existing information on this topic. The region is particularly challenged by a number of factors, including the large variability of bio-geographical characteristics, extreme population growth over the last few decades, and substantial societal and economical transitions, as well as armed conflicts in some of the countries in the region. Anticipated changes in climate conditions will exacerbate the challenges regarding water and energy security in the region. Major impacts of climate change include a significant increase in summer temperatures, which will lead to a growing number of heat waves, primarily in urban structures. A general decrease in precipitation in many of the MENA countries is foreseen, resulting in enhanced droughts and a growing number of dry spells. In addressing energy and water scarcities and their mutual interrelationships, an integrated water–energy nexus concept offers promising prospects to improve environmental, climate, human, and political security. However, only very few countries in the MENA region have presently implemented such a concept. Mitigation and adaptation strategies addressing water and energy scarcity include enhanced efficiency of resource use, integrated technology assessments regarding electricity generation, and a stronger reliance on renewable/solar technologies. While looking at the MENA region as a whole, some emphasis will be given to Cyprus and the Eastern Mediterranean.