Tourism is a strategic sector for the Portuguese economic and social development in general, and for Setúbal municipality in particular. Consequently, the existence of an effective ecosystem that promotes competitive business is crucial for the region. This chapter considers how the entrepreneurial ecosystem concerning tourism sector is perceived and operates in this Portuguese municipality. The authors chose a case study research strategy, in addition to documental analysis, through which we selected 45 stakeholders to participate as a focus group, related to the entrepreneurial activity in tourism in the municipality. The evidence shows that Setúbal municipality has relevant ecosystem elements, which are determinant for the development of the tourism entrepreneurial activity in this region. However, it is not functioning systemically in a way that can generate more effective results in the entrepreneurial activity. This result is also related with the fact that tourism activity in the region is in an initial phase and it is expected that, with its continuous development, the entrepreneurial ecosystem will also grow and become stronger, being able to create more synergies that will support new businesses.