The onset of industrialization to meet socioeconomic demands has placed significant stress on the environment. Human activities have led to critical levels of climate change and environmental degradation. Such pressures pose severe risks to biodiversity, altering species distribution and abundance. Globally, the rapid loss of biodiversity is alarming, signalling a biodiversity crisis. In Botswana, the rich ecological resources are also rapidly depleting due to human impacts. There is a pressing need for sustainable environmental governance that balances ecological and socioeconomic requirements. Sustainable solutions depend on the prudent use of ecological resources. Effective conservation in human-dominated ecosystems relies on creating beneficial linkages. This chapter introduces nexus thinking—an approach akin to systems thinking—for biodiversity conservation, emphasizing the principle of “thinking globally, acting locally”. It examines nexus thinking as it relates to the interdependencies among conservation, livelihoods, and biodiversity in the Mokolodi Nature Reserve (MNR) in Botswana. These elements form a complex, interconnected system that could uphold ecological integrity and foster sustainable local development. Implementing this interactive model could enhance resource security and promote sustainable development, offering a promising framework for addressing environmental challenges in human-dominated ecosystems.