This chapter examines how geographical factors shape the performance of Japan’s Regional Innovation System (RIS), focusing on domestic patenting activities. Using prefectural-level panel data from 2000 to 2018 and applying a dynamic panel model based on difference generalized method of moments estimation, the analysis assesses the influence of industrial clusters, transportation infrastructure, and interregional accessibility (Borrowed Size) on the quantity and efficiency of patent output. The results indicate that employment density and establishment size positively affect patent activity, whereas total employment has a negative effect, suggesting that innovation is driven not by labor scale but by the spatial concentration of knowledge-intensive activity. Furthermore, transport capital and interregional accessibility contribute positively to innovation. Moran’s I tests reveal no significant spatial autocorrelation in patent outcomes, indicating that domestic innovation in Japan tends to remain geographically bounded within regional units. These findings have several policy implications. In the context of demographic decline, fostering innovation hubs through dense knowledge environments and infrastructure investment may be more effective than general employment expansion. Additionally, the spatially localized nature of domestic patenting underscores the need for place-based strategies that strengthen local innovation ecosystems while recognizing the limited potential of interregional spillovers.