The paper examines the evolution of Vietnam STI policy from the cultural approach to STI Policy by analyzing the role of various policy cultures representing the government, research, industry and civil society in codeveloping STI Policy in dealing with emerging grand challenges and uncertainties. It argues that the policy evolution from the research policy to transformative innovation policy in Vietnam depends on the dynamic interaction among those four co-existing policy cultures/domains in shaping the STI policy and defining alternative pathways to sustainability, each with potential for setting a trajectory for systemic change. Selected transformative innovations in dealing with covid 19 and climate change related risks are presented to illustrate the imperative of experimenting those pathways by various policy actors with different motivations and priorities. The paper concludes that Vietnam as later developer could share its experience in dealing with grand challenges through developing an inclusive, transformative and climate change resilient STI policy.