Lake Victoria’s thriving blue economy has provided a livelihood for half a million individuals in Kenya, Tanzania, and Uganda in the past. However, climate change, pollution, invasive species, declining fish stocks, and water inlet interference have threatened the lake’s potential, resulting to cage farming as a means to rear fish through climatic disruptions. Furthermore, climate change alters environmental conditions and disease dynamics, thus posing significant impacts to aquaculture. Higher water temperatures coupled with extreme weather events can worsen pathogen risks and stress farmed aquatic animals, making them more susceptible to disease. Coupled with rising intensification of cage culture, there is need for enhanced adaptation strategies to cope with changing environmental conditions for long term sustainability of livelihoods of fishermen and fish farmers. To ensure an appreciable level of disease prevention and control, effective biosecurity strategies, increased capacity building, comprehensive policy and regulatory provisions are a necessity for sustainable livelihoods for fisher-folk in Lake Victoria region.