The rise of global competitors operating at a lower cost, trade restrictions caused by the US-China dispute and local content requirements, and eroding margins in many product businesses all exert downward pressure on industrial firms’ profitability. This is further exacerbated by the short- and long-term economic consequences of the COVID-19 pandemic. A crucial lesson manufacturers learned is that value chains need to be more resilient toward external shocks. Production processes need to become more flexible to adjust for short-term changes in demand, and customer support has to be ensured even when travel restrictions apply. Industry 4.0 and smart manufacturing and services hereby play a crucial role in reaching these goals and are much better prepared for future challenges. The underlying article elaborates upon this matter and most crucially unfolds upon the pathways toward smart manufacturing and services. Finally, valuable success factors for managing and operating within the Industry 4.0 domain are stated.