Sustainable development is considered as one of the vital challenges of the 21st century for humanity. The COVID-19 pandemic has disrupted economic and social life, forcing governments and businesses to reconsider their priorities. There are rare empirical studies on the national innovation system and its relationship to sustainability development for emerging countries. This paper aims at shedding light on how mission-oriented policies have marked sustainable regional development and innovation in Latin America. The present study presents the capabilities that could support the improvement of the national innovation system and, as a consequence, sustainability development. To understand how Latin American countries act on innovation and sustainable development initiatives, two global rankings in these areas, The Global Innovation Index 2020 and The Sustainable Development Report 2020, were analyzed. The results indicate some obstacles must be overcome such as the high levels of social inequality and poverty that still constitute significant challenges for this region. Today’s biggest challenges are facing a pandemic situation and guaranteeing economic development that allows the underprivileged to escape poverty without dooming future generations to an even more degraded environment than the current one. Innovation continues to play a critical role in the transition toward a more sustainable world.