This Expo book brings together leading academic and policymaker experts to reflect on the significant challenges faced by lagging regions in participating in the European Union’s Research and Innovation Strategies for Smart Specialisation (RIS3) programme. In doing so, the book offers a set of new policy recommendations on the design and implementation of appropriate Smart Specialisation Strategies (S3) in lagging regions, which may enable them to benefit from the opportunities of digitalisation and Industry 4.0 (I4.0).