Settler colonialism and neoliberalism have impacted the Australian health system’s ability to engage in authentic approaches to Aboriginal and Torres Strait Islander health and wellbeing. This chapter reflects on the historical socio-political context of health system policy and explores how this influences current strategic agendas in Indigenous health policy, workforce, services and research. Reflecting on the influence of Humphrey’s Indigenous Research Reform Agenda in strategically strengthening the Indigenous research health agenda, we then outline an argument for a similarly strategic approach to health system reform. In doing this we have drawn on the foundations of Indigenist Research Methodologies to outline a framework for an Indigenist Health System Reform Agenda grounded in Indigenous sovereignty. Finally, we outline a call to action to formulate a systems response through an Indigenous collective that progresses Indigenous Knowledge Translation to enable a just health system that is grounded in Indigenous Knowledges.