Boosting the externalities across the water, energy, food, and waste (WEFW) sectors is challenging, especially considering tightening constraints such as population growth, climate change, resource-intensive lifestyles, increased waste production, sanitary crises and many others. The nexus approach supports the transition to a more sustainable future because intersectoral trade-offs can be reduced and externalities exploited, making imperative for decision makers, entrepreneurs, and civil society to simultaneously engage, with respect to all the components of the nexus. This research addressed intersectoral synergies and trade-offs in the case of the WEFW nexus in Romania, judging from the perspectives of entrepreneurial activity and economic results. The objective of this research was to explore the nexus in-depth by statistically analyzing the financial and economic indicators reported by active enterprises at county-level, based on the Romanian Ministry of Public Finance data. Research results describe the effects of the policies implemented in the fields of WEFW sectors. At the same time, attention was paid to the quality of the entrepreneurial activity, analyzed from the perspective of economic performance. This paper fills a research gap regarding the WEFW nexus by resorting to an economic and entrepreneurial performance assessment in order to find sectoral pathways toward policy cohesion in Romania. Findings suggested the existence of major trade-offs among sectors, owing to the fact that each county has a different development degree.