Unarguably, smart, sustainable, and knowledge-based development is critical for securing a livable future for our rapidly urbanizing world. The aim of this study is to generate insights into determining effective and efficient strategies to increase sustainability and innovation capabilities of cities to achieve long-term desired urban outcomes. This paper places the city of Florianópolis (Brazil) under the smart, sustainable, and knowledge-based urban development microscope. The methodological approach of the study involves a qualitative analysis through surveys (100 submitted forms, 55 responses received) and interviews (12) with key experts and stakeholders from Florianópolis. The findings of the study reveal that Florianópolis’ innovation ecosystem has high potential to thrive, but the city still has structural issues to deal with first, related to the gap between the potential to grow, and acknowledgement from key actors of the city to support the overall territory development considering the complex dimensions. This issue suggests amplifying the ecosystem’s vision, including different sectors and, especially, addressing innovation for the common good. The insights generated from the investigation of Florianópolis’ case are also invaluable to other cities’ planning for strategizing their transformation, and seeking smart, sustainable, and knowledge-based development pathways.