In the light of several national advanced manufacturing strategies such as Industry 4.0, this article examines the challenges of Industry 4.0 adoption of Latin American small and medium-sized manufacturing firms (SMEs).The future of Industrial systems that has encompassed so many investigative processes in the last decade, surrounds the fourth industrial revolution, which covers the Internet of Things, Augmented Reality, real-time connection, Data Mining, Big Data, Cloud computing, Cyber Physical Systems (CPS), among others. The reality is that the majority of industries that have implemented these technologies are those large-scale companies with great leverage and long-term investment power. The development of this so-called Fourth Industrial Revolution is disconnected from the SMEs, despite the fact that in Latin America they represent more than 95% of registered companies. In this study, an analysis of scientific publications on small and medium-sized companies is carried out, in addition, some variables necessary for the real measurement of the application of Industry 4.0 in Latin America are proposed. Flexibility, quality, competitive advantage and cost benefit were key variables to create a suitable model to be implemented in SMEs.