Doing business in the climate change context can be challenging today. Businesses are impacting the environment through their production processes, while simultaneously becoming vulnerable to the effects of the climate crisis. Businesses can potentially facilitate climate change mitigation and adaptation by implementing clean technologies, which in turn offer business opportunities and open venues for new markets. However, studies indicate that business responses to climate change are not treated with the importance the matter deserves. They are slow in responding with effective action, and relatively few companies have been able to completely integrate climate change matters into their business strategies. In the last decade, the international community has made appeals to adopt systemic responses to climate change and resource scarcity. Under this concern, the water-energy-food (WEF) nexus has emerged as a new approach—the nexus approach—that seeks to understand the interdependencies, synergies, and tradeoffs of natural resources interrelationship and management. In this chapter, we explore the Brazilian ethanol case focusing on water, land, and food sustainability practices. A study of bioenergy business cases incorporating the concepts of the WEF nexus contributes to the expansion of understanding the necessary interdependencies and relationships among nexus resources in bioenergy production.