The 2020s is on track to become one of the most transformative decades in human history. On the one hand, numerous mature technologies will have their mainstream breakthrough in the years to come. As these are combined in various and innovative ways, all human endeavours are likely to be transformed. This has been talked about in terms of the fourth Industrial Revolution. On the other hand, unchecked exploitation of human resources, particularly in the form of climate change, needs to be efficiently dealt with during the 2020s. The United Nations has stipulated a strategic plan, Agenda 2030, to deal with these, including a strict deadline at the end of the decade. Curiously, few academic researchers work with both the fourth Industrial Revolution and Agenda 2030. The imperative of combining strategic work on these is in this article called the challenge of challenges. The chapter is concerned with the articulation of this meta-challenge as well as discussing the role of academic research, more specifically that of information science. It is argued that information science is well situated to make substantial contributions to the challenges of challenges. Three distinct areas within such contributions are outlined: sustainable targets/indicators, open science, and sustainable information literacies.