In African nations, national and regional development targets for water and energy sectors seldom consider the nexus between the two, risking imbalances and inefficiencies in resource allocation and utilization. A typical example is the development and expansion of biofuel in the Wami Ruvu River Basin, Tanzania (WRB). Water Evaluation and Planning (WEAP) model was applied to the WRB to investigate the Water Energy Nexus (WEN), specifically, whether the development plan calling for biofuel expansion is a sound approach. Results show that WEN is much stronger in the biofuel irrigation consuming 69.3% and 61% of total biofuel's water and energy requirement, respectively. By 2035, the nexus continues to be stronger, consuming 54.5% and 49% of total biofuel's water and energy requirement, respectively, and thus first generation biofuels use much more resources in the growing than the refining process. An additional 768.2 million meter cubic of water and 413.4 million kWh of energy are needed for planned biofuel expansion, reallocating water to biofuels in water-scarce regions inherit related problems to other sectors such as increasing water use for the industry, agriculture, and energy sector by 67%, 45%, and 9%, respectively, which could further exacerbate stresses on water and energy supplies in the basin. Biofuel generation rely heavily on energy imports, as it consumes substantially more energy than it produces. Policies should promote the coordinated development of sustainable biofuel programs that are less water intensive with very low inputs of fossil fuels.