Water-energy-food (WEF) nexus is a concept that aims at integrating these three key economic drivers which are very crucial for the improving the livelihood of the people, general economic sustainable development and social well-being of the world population. The effective utilization and management of these key resources require in-depth planning assessment of symbiosis, competitions and concession with an essential contribution in the nexus. This paper aims at reviewing the WEF in the Great Lakes region of Africa with a focus in Kenya, Democratic Republic of Congo, Rwanda and Uganda. The status and prospects in each country has been assessed and the interconnection between the three fundamental resources together with the effects of climate change towards the security of these resources in the selected countries have been discussed. The review has found out that the selected countries are indeed WEF insecure since the impacts of climate change and poor infrastructure play a vital role in the insecurities highlighted. In the focused countries, it was realized that the existence of weak institutional and legal frameworks, political instability and poor infrastructure indeed hinders the regional attainment of the WEF nexus for sustainable economic development. This therefore calls for a dire need for the adoption of climate change adaptation and mitigation measures in the WEF nexus through an integrated and holistic approach in the Great Lakes Region of Africa.