This chapter explores how innovation ecosystems within Romania’s CENTRU Region foster intelligent and sustainable regional growth by encouraging technology transfer, modernization in education, and progress in digitalization. Drawing on a comparative case study approach, the analysis focuses on three European Union (EU)-funded initiatives that highlight different routes toward regional transformation. These include an educational infrastructure program designed to boost energy efficiency and vocational skills, a digital recruitment platform aimed at strengthening the competitiveness of small and medium-sized enterprises (SMEs), and a Smart City Living Lab (SCLL) that encourages technology exchange and collaborative innovation. The discussion uncovers shared factors that enable or hinder progress, along with the adaptive responses developed locally. Particular attention is paid to governance capacity, digital readiness, and institutional partnerships as key elements for sustainable regional development. Overall, the study shows how the principles of smart specialization (RIS3) and the circular economy can be translated into practice through integrated investments that connect innovation, skills, and social inclusion, contributing to a broader understanding of the European Union’s dual green and digital transition.