The present paper discusses perspectives of Activity Theory (AT) in the context of contemporary globalizing world, describing which we refer to the notion “De-structuralized modernity” (Sorokin and Froumin 2020). Radical changes in everyday life challenge social sciences and humanities. Approaches are in demand, which have the potential to comprehend the changing human étant and éntre. We argue that Activity Theory has the potential to face these challenges. Leontiev’s AT grounds on the idea of qualitatively new mental features arising to deal with novel environmental challenges, which is much in line with J.M. Baldwin reasoning on evolution. AT also offers a method to prognosis the upcoming neoplasms. In the same time, applying classics of AT to the current reality, “De-structuralized modernity”, entails the need for new theoretical elaborations of the latter, stemming from the radical transformation of the relations between individual and socio-cultural environments. A unique societal context emerges on the global level, which, on the one hand, requires individual to adapt constantly to changing socio-cultural reality, and, on the other hand, dramatically expands his/her potential for proactive actorhood transforming surrounding structures. We argue that the major and novel challenge for the individual is that maintaining the integrity and coherence of the a) Self-identity and b) system of links with the socio-cultural environment - in their dynamics and unity, has become a qualitatively different issue, much more complicated and problematic than ever before. The notion of “culture” has particular relevance and importance in this context because it allows grasping simultaneously two dimensions in their dynamic dialectical interrelations. First, the “internal” (“subjective”, “in the minds”) and “external” (“objective”, material and institutional environment) realities. Second, individual (“micro”) and societal (“macro”) scales of human activities. Discussing the ways to understand these dynamics, we dispute the popular “constitutive view” on personality and refer to the concept of the “ontological shift” (Mironenko and Sorokin 2018). We also highlight how technological advancements change and “expand” human nature making it capable to deal with the outlined new tasks.