Despite consensus on the transformative potential of science, technology and innovation (STI), there remains a lack of clarity on how Least Developed Countries (LDCs) can effectively implement it for inclusive and sustainable development. This publication highlights four key innovation policy options which have the potential to enable LDCs to reap the benefits of innovation in a cost-effective manner. First, LDCs must mobilize all available talent towards sustainable development if the ambitions of the 2030 Agenda are to be met. Second, the rule of law and STI are inextricably linked. An enabling environment that encourages and protects risk-taking, and a secure investment climate are vital components of an innovation system. Third, it will be critical to incentivize investment from sources such as foreign direct investment (FDI) and impact investment and align all available sources of STI finance towards sustainable development. Fourth, creating open and inclusive innovative knowledge economies will be critical. Enabling international mobility, international technology transfer and participating in the regional and global innovation agendas will support national innovation capacity development.