New and residual challenges related to digital technology, COVID-19, precarious employment and scientific management are a reminder of research published in the early years of Human Relations that laid the foundation for socio-technical systems theory and its later conceptual offspring, the quality of working life. Analysing the evolution, challenges, legacy and lessons of socio-technical systems and quality of working life, we develop guiding principles for the theoretical development and practical implementation of socio-technical systems and quality of working life for the 21st century. These principles are needed to optimize the benefits of new technology and improve job quality. They would enable an effective and sustained humanization of work through stakeholder involvement, inter-disciplinary partnerships and institutional support, producing positive outcomes for employees and employers as well as wider society.