This paper aims to propose a process-oriented and integrated framework for designing mission-oriented innovation policies to address grand challenges. The main problem is the inefficiency of traditional and fragmented policies in dealing with these multi-dimensional and interconnected issues, which necessitates a systematic approach. Furthermore, previous efforts in this field, despite their strengths, have certain shortcomings that justify the development of a combined framework. In response to this gap, the article presents a nine-stage framework: Formulating the grand challenge and its dimensions, Defining missions, Identifying influential and affected sectors, Identifying actors and stakeholders, Determining key functions and institutional mapping, Defining research and innovation projects, Designing a policy mix, Establishing governance and implementation mechanisms, and Designing a monitoring, evaluation, and learning system. With features such as a step-by-step approach, cross-sectoral governance, integrated planning, the integration of science and policy, continuous learning, and active market shaping, this framework moves beyond fragmented policymaking and offers a systematic solution for confronting grand challenges.