question: Global urban population exceeded rural population for the first time in history in 2008, and the United Nations forecast that 66% of the world’s population will live in urban areas by 2050. In Latin America, urban growth will be exceptional, and the forecast is even bigger, that is, 83% in 2030. Cities will consequently be the locus of major challenges like air pollution, traffic congestion, water, and waste management. They will also have to offer economic activity and good well-being for these immigrants coming from the rural zones looking for job opportunities. In this chapter, we develop the five major challenges we believe cities will face as corroborated by other authors. These are short-term issues related to the environment, economic competitiveness, and the quality of life offered but also long-term issues covering resilience and sustainability problems. At present, we are living through an overwhelming sanitary and financial crisis linked to the COVID-19 pandemic crisis. This book is not aimed at just discussing and measuring specific effects on the global economy and people health conditions. We have indeed embraced a wider and larger objective of reflection. Nevertheless, we have included in the following paragraphs the start of analysis of its possible effect.