Mission-oriented innovation policies (MOIPs) offer a strategic approach to address complex societal challenges like climate change, health crises, and digital transformation. For MOIPs to succeed, tailored governance structures are essential, enabling coordination across sectors and policy areas. This policy paper identifies key governance challenges, such as overcoming institutional silos, integrating funding streams, and managing trade-offs in leadership. It highlights the need for adaptive, flexible governance mechanisms that evolve alongside the mission‘s life cycle. The paper proposes a framework of five core governance principles: structure, orientation, coordination, implementation, and resources. By following this framework, policymakers can design effective governance systems that align with the mission‘s theory of change, ultimately enhancing the transformative potential of MOIPs. The recommendations emphasise viewing mission governance as a critical enabler, fostering collaborative and impact-oriented policymaking to tackle complex issues.