The paper aims to develop and apply a methodological approach that could help to reveal incentives and future strategies of key National Innovation System (NIS) players considering the influence of global social, economic, scientific, technological and ecological trends. To fulfil this aim, a blended foresight methodology was applied, grounded on the platform of economic and classic foresight theory and considering four possible directions for using foresight methods: investigating and building a common vision; supporting evidence-based decisions; promoting communication and participation; inducing transformation and integration into the decision-making process. The main results and findings of the research include a list of 19 global trends, defined from literature analysis and the author’s expert knowledge, a short description of their influence on key NIS players, including society, business, infrastructure and institutions, science, education and government; and mapping more than 35 different foresight methods that could be used for revealing incentives and future strategies of key NIS players. The article’s theoretical contribution to economic theory consists of several parts. First, a NIS conception is examined through the prism of global trends and a dynamic aspect, whereas it is mostly investigated from statistical and static perspectives. Second, applying foresight as an instrument for researching NIS as a system is a developing academic area with some theoretical gaps, considered in this article by designing a conceptional research framework. Third, blending different foresight methods is always a craft, and the approach applied in this article contributes to it. Finally, the article presents several important trends which will appear in NIS and its key players’ transformation in the nearest 5–10 years. From practical implications, this article could be useful for proactive policymakers in the field of science, technology and innovation policy at national and regional levels for designing and providing measures for supporting innovation systems effectively. Foresight practitioners and experts are offered useful, practical ideas of different foresight methods and their possible combinations for everyday activities.