The global demand for sustainable protein sources—driven by population growth, climate change, and increasing pressure on conventional agriculture—has intensified the search for innovative, eco-friendly production methods. Post-distillation wine lees (vinasse) remains a largely underutilized byproduct of the wine and distillery industries. For every liter of ethanol produced, approximately 9–14 liters of vinasse are generated, creating a pressing need to manage trillions of liters annually. Due to its composition—particularly its high polyphenolic content and chemical oxygen demand—vinasse poses significant environmental and public health risks if not properly treated. This study presents a novel bioconversion strategy to valorize vinasse by cultivating protein-rich fungal biomass through submerged fermentation, using edible Ascomycetes and Zygomycetes filamentous fungi. The proposed biorefinery approach not only mitigates waste management challenges but also offers a scalable and sustainable pathway for alternative protein production. By converting a problematic effluent into a valuable resource, this bioprocess contributes to the development of circular, climate-smart food.