This chapter advances a Schumpeterian reinterpretation of evolutionary economic geography by placing entrepreneurial ecosystem emergence at the center of regional economic transformation. It argues that regional development is driven not by incremental adjustment along inherited paths, but by creative destruction organized through entrepreneurial agency, innovation-induced disruption, and institutional reconfiguration in place. Entrepreneurial ecosystems are conceptualized as spatially embedded selection environments that shape the generation, selection, and retention of novelty. From this perspective, uneven regional development and resilience are endogenous outcomes of capitalist evolution, reflecting differential capacities for recombination, renewal, and transformation under uncertainty.