Dominant and quite restricted approaches to Industry 4.0 paint a bleak scenario for industrial districts, suggesting that they might be doomed to decline or to becoming dependent on large technological companies. This chapter illustrates how Industry 4.0+ can support transformative pathways leading to the upgrading and rerouting of local productive systems of small and medium-sized enterprises (SMEs) following the diffusion of the digital technologies linked to the Fourth Industrial Revolution. The economic and social sustainability of such systems is not necessarily guaranteed since the auto-reproductive capabilities they rely on are likely to be modified. In fact, the nature and dynamics of districts’ external economies will adapt as local systems of SMEs experience new solutions to be competitive and successful in the global markets. Depending on the wealth and composition of specialised knowledge bases and on the breadth of its local business networks, a local productive system can embark on different types of learning processes.