With the advent of disruptive digital technologies, companies are facing unprecedented challenges and opportunities. Advanced manufacturing systems are of paramount importance in making key enabling technologies and new products more competitive, affordable, and accessible, as well as for fostering their economic and social impact. The manufacturing industry also serves as an innovator for sustainability since automation coupled with advanced manufacturing technologies have helped manufacturing practices transition into the circular economy. To that end, this Special Issue of the journal Applied Sciences, devoted to the broad field of Smart Sustainable Manufacturing Systems, explores recent research into the concepts, methods, tools, and applications for smart sustainable manufacturing, in order to advance and promote the development of modern and intelligent manufacturing systems. In light of the above, this Special Issue is a collection of the latest research on relevant topics and addresses the current challenging issues associated with the introduction of smart sustainable manufacturing systems. Various topics have been addressed in this Special Issue, which focuses on the design of sustainable production systems and factories; industrial big data analytics and cyberphysical systems; intelligent maintenance approaches and technologies for increased operating life of production systems; zero-defect manufacturing strategies, tools and methods towards online production management; and connected smart factories.