The City of Manchester, once the birthplace of the 1st Industrial Revolution, is today a pioneering hub of the 4th Industrial Revolution (Industry 4.0), offering Industry 4.0 solutions in advanced materials, engineering, healthcare and social sciences. Indeed, the creation of some of the city’s greatest academic institutions was a direct outcome of the industrial revolution, so it was something of a homecoming that the Sustainable Smart Manufacturing (S2M) Conference was hosted by The University of Manchester in 2019. The conference was jointly organised by The University of Manchester, The University of Lisbon and The Polytechnic of Leiria – the latter two bringing in a wealth of expertise in how Industry 4.0 manifests itself in the context of sustainably evolving, deeply-rooted cities. S2M-2019 instigated the development of 61 papers selected for publication in this book on areas of Smart Manufacturing, Additive Manufacturing and Virtual Prototyping, Materials for Healthcare Applications and Circular Economy, Design Education, and Urban Spaces.