In Ethiopia, land, water, energy and food (LWEF) nexus resources are under pressure due to population growth, urbanization and unplanned consumption. The effect of this pressure has been a widely discussed topic in nexus resource literature. The evidence shows the predominantly negative impact of this; however, the impact of these factors is less explored from a local scale. As a result, securing nexus resources is becoming a serious challenge for the country. This necessitates the identification of the driving factors for the sustainable utilization of scarce LWEF nexus resources. Our study provides a systemic look at the driving factor indicators that induce nexus resource degradation. We use the Analytical Hierarchical Process (AHP) to develop the indicators’ weights, and use a Path Analysis Model (PAM) to quantitatively estimate the effect of the driving factor indicators on the LWEF nexus resources. The results indicate that social (48%), economic (19%), and policy and institutional changes (14%) are the major nexus resource driving factor indicators. The path analysis results indicate that among the social driving factor indicators, population growth and consumption patterns have a significant direct effect on the LWEF nexus, with path coefficients of 0.15 and 0.089, respectively. Similarly, the potential of LWEF nexus resources is also influenced by the institutional and policy change drivers, such as outdated legislation and poor institutional structure, with path coefficients of 0.46 and 0.39, respectively. This implies that population growth and consumption patterns are the leading social drivers, while outdated legislation and poor institutional structures are the institutional and policies change drivers which have a potential impact on LWEF nexus resource degradation. Similarly, other driving factors such as environmental, economic and technological factors also affect nexus resources to varying degrees. The findings of our study show the benefits of managing the identified driving factors for the protection of LWEF nexus resources, which have close links with human health and the environment. In order to alleviate the adverse effects of driving factors, all stakeholders need to show permanent individual and collective commitment. Furthermore, we underline the necessity of applying LWEF nexus approaches to the management of these drivers, and to optimize the environmental and social outcomes.