This article aims to address the challenges of sustainable earth system governance from a multi-scale level perspective. The local to regional system level reviews findings from a social–ecological system approach of a mangrove ecosystem in North Brazil. Seven challenges (Glaser et al. in Mangrove dynamics and management in North Brazil. Ecological studies series. Springer, Berlin, pp 307–388, 2010) that could provide relevant knowledge to society were identified. Their respective justification and recommendations are presented here. Further, these “challenges from the field” are linked and discussed with those challenges on earth system level elaborated by the International Council for Science in 2010. There it was stressed that sustainability problems are increasingly caused by drivers from multiple spatial and institutional levels in a single global human–nature system. The comparison between the global and local to regional challenges shows that most of these are reappearing disregarding the level of analysis, indicating that there is a universal core of global change problems. However, there are gaps visible which hamper the effective connections across the different spatial levels. These pertain to the subjects of knowledge generation and stakeholder inclusion. The final section elaborates on these recognized gaps and their science–policy dimensions. The article closes with the identification of a number of factors which currently impede global sustainability efforts: shortcomings in inter- and transdisciplinary research practice, lack of consistent structures for earth system governance and shortcomings in dealing with upscaling challenges whilst remaining locally relevant. A blueprint for a globally focused but regionally informed social–ecological analysis framework remains to be worked out.