The rapid change of technological, social, and cultural structures is challenging universities to offer new educational programs. The Global Leader Program for Social Design and Management (GSDM) of the University of Tokyo can be seen as a forerunner in this field. The paper provides definitions of social design as well as of global leadership and provides a proposal for the definition of the objective of the GSDM program, i.e., multi-level resilient human–environment system. These subjects are embedded in the framework of human–environment systems (HES). We identified the different types of knowledge integration that ‘global leaders for social design’ should master. The core of a sustainable social design is to (1) properly conceptualize and manage “resilient coupled human-environment systems” and to (2) integrate or relate different systems, epistemics, interests, cultures, and knowledge systems. The specific challenge in this context is to cope with conflicting cultural–religious systems or to understand how the vulnerability of different human systems with respect to digital environments. Social design is conceived as all rules, mechanisms, and preferences that govern the interaction of humans with material, biophysical, technological, and socio-cultural epistemic environments. The goal of education for global leadership for social design may have to progress from the T-shaped skills profile (i.e., being specialized in one discipline and having the capability to collaborate with other disciplines) to the π-profile. Students for leadership in global designs must be qualified in a social and an engineering/natural science and literate and capable to know, relate, and govern different disciplines, cultures, or systems which have to be included in the sustainable transitioning of cultural and socio-technological systems. The paper elaborates in what way transdisciplinarity is needed and why resilience management should be seen as a proper objective of GSDM. The challenges of the new educational program for the science system and institutions as well as for students and professors are discussed.