This study analyses the contribution of territorial sensitive resources related to natural and cultural features (environmental dimension), innovation capabilities and specialization patterns (smart specialization) to regional sustainable development (spatial sustainability). In the context of a fast and continuous expansion of tourism activities, particular attention is given to their impacts. The results of our path model suggest that different patterns of tourism dynamics coexist in European regions and that, for those where this sector assumes larger socio-economic importance, the contribution to the achievement of the “Millennium Goals”, as proposed by the United Nations, is relatively poor. Regions particularly endowed in natural resources reveal a weak socio-economic performance, while showing high levels of specialization in tourism, based on large scale and low value-added products and services, suggesting that new approaches to territorial design are required. This also leads to important spatial unbalances, with the most tourism-dependent European regions revealing relatively low levels of regional gross domestic product and high levels of unemployment. Despite their relatively good performance in terms of CO2-emissions, it seems important for those regions' sustainable development to increase the value added in tourism, by reinforcing the linkages with other relevant regional economic sectors. Information and communication technologies can contribute to these achievements, through the integration of knowledge and innovations into the products and services comprising the smart tourism experiences (smart development) and their connections with related sectors (smart specialization).