The development of high-speed rail (HSR) in Italy has garnered significant investment, especially in the southern regions. One important infrastructure project that aims to connect the regions of Campania and Puglia as well as the cities of Naples and Bari to Rome is the Naples-Bari or “Na-Ba” line. The “Na-Ba” project aims to enhance accessibility and connectivity, particularly for inland areas between Avellino, Benevento and Bari, which are important hubs for both tourism and production but currently face significant accessibility challenges. While major urban centres, as Naples and Bari, are expected to directly benefit from the HSR line, the potential impacts on more rural areas remain uncertain and warrant further investigation. The study methodology is structured in two phases. The first phase involves an analysis of accessibility, focusing on key variables relevant to tourism, such as transport access, services, and service frequency. The second phase consists of a scenario-based comparison (“as is” vs. “to be”), utilizing an econometric model to explore the relationship between HSR and local economic growth, particularly in the tourism sector. The results from the econometric analysis indicate a steady increase in tourism-related investment across different scenarios of intermodality. In Scenario 1 (Low Intermodality), predicted investment levels reach 9.44, while Scenario 2 (Medium Intermodality) estimates 9.52, and Scenario 3 (High Intermodality) projects an investment of 9.63. The findings also show a 3% improvement in accessibility, and increased transport service frequency has a positive impact on tourism investment.