Drawing inspiration from the works of Fiorenza Belussi on multiple paths of development in local productive systems, the essay contributes to the ongoing debate on factors facilitating such transformations, focusing primarily on industrial districts (IDs) as open learning systems. With specific reference to the Italian context, this paper recalls the delicate balance between socio-cultural and economic elements within IDs transitioning towards new paths of development, crucial for facing the current technological and societal challenges. The essay proposes to look at the possible diffusion of humanistic management (HM) and cultural enhancement of economic strategies, as new triggering factors against lock-in conditions and tendencies toward degradation during phases of ID transformation. HM prioritizes the well-being of individuals and ethical decision-making, aligning with a broader societal purpose. Cultural enhancement, rooted in a common heritage, supports place identity, and suggests bases for multiple specializations. The convergence of HM and cultural enhancement within IDs may offer to renewed place-leaderships levers for strategies of transition pointing to sustainable paths that align with broader societal goals in an era of disrupting challenges.