The integration of AI with software is an essential enabler for science and the new economy, creating new markets and opportunities for a more reliable, flexible and robust society. Current software methodologies, tools and techniques often fall short of expectations, however, and much software remains insufficiently robust and reliable for a constantly changing and evolving market. This book presents 54 papers delivered at the 20th edition of the International Conference on New Trends in Intelligent Software Methodology Tools, and Techniques (SoMeT_21), held in Cancun, Mexico, from 21–23 September 2021. The aim of the conference was to capture the essence of a new state-of-the-art in software science and its supporting technology and to identify the challenges that such a technology will need to master, and this book explores the new trends and theories illuminating the direction of development in this field as it heads towards a transformation in the role of software and science integration in tomorrow’s global information society. The 54 revised papers were selected for publication by means of a rigorous review process involving 3 or 4 reviewers for each paper, followed by selection by the SoMeT_21 international reviewing committee. The book is divided into 9 chapters, classified by paper topic and relevance to the chapter theme. Covering topics ranging from research practices, techniques and methodologies to proposing and reporting on the solutions required by global business, the book offers an opportunity for the software science community to consider where they are today and where they are headed in the future.