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While knowledge has long been central to theories of innovation-led regional development, its con-
ceptualization within the emerging transformative innovation paradigm has remained largely implicit
and undertheorized. This paper draws on insights from sustainability transitions, organizational
learning, and higher education studies to develop a perspective on the action-oriented nature of
knowledge, as it increasingly associates with the matters of directionality, materiality and structu-
ration. Based on this, we articulate an idea of transformative knowledge through a triple lens, empha-
sising interdependencies between knowledge for action (goal- and mission-oriented), knowledge by
action (generated through experimentation), and knowledge as action (situated in practice and every-
day life). We apply this lens to discuss the outlines of transformative knowledge regions, proposing an
expansion in the repertoire of regional innovation interventions. In doing so, the paper broadens the
epistemic contours of knowledge in regional development and contribute to current debates on chal-
lenge- and mission-oriented regional innovation policy.