This paper explores how the mission-oriented approach (MOA) can be embedded into the existing policy framework, especially at the local level, by focusing on the specific case of smart specialization strategies (S3s). In response to mounting pressure to shift from a competitiveness-driven paradigm to one oriented at tackling societal challenges, regional innovation strategies such as S3s have increasingly claimed to incorporate MOA elements. Against this backdrop, the paper investigates, through a policy practice lens, whether the S3 framework can integrate MOA characteristics seamlessly, and what frictions or challenges may arise in doing so. We develop an analytical framework grounded in the core features of MOA and apply it to three S3 case studies with transformative innovation ambitions: Catalonia, Northern Netherlands and Brussels. Our findings indicate that reorienting regional innovation strategies towards a mission-led or challenge-driven logic involves trade-offs between strategic directionality and bottom-up flexibility as well as administrative autonomy and political accountability. Additionally, we identify persistent challenges in effectively engaging actors with a long-term perspective, aligning strategies with other policy domains and designing appropriate instruments because of compliance-oriented cultures, rigid rules and path dependence.
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