The orientation towards grand societal challenges can be seen as a new wave or paradigm for innovation policy. Such policy aims at system-wide transformation and is often referred to as system innovation policy. While insights from transition studies have provided novel and useful rationales for innovation policy targeting system-wide transformation, it remains unclear how to design, implement and evaluate such policies. The contribution of this paper is to translate and concretize the challenges of system innovation policy towards scope for policy action and analysis. Building on insights from transition studies we group the challenges into four domains: directionality, experimentation, demand articulation, and policy coordination and learning. We relate challenges within the four domains to three generic features of innovation systems: interests and capabilities of actors, networks, and institutions. The derived framework is applied in a case study on the strategic innovation programmes, a recent policy initiative by Vinnova, Sweden's Innovation Agency, targeting system innovation.