A recent development in the tourism industry is integrating smart technology into prominent destinations to provide personalized experiences for visitors and improve their satisfaction. As a result of smart destinations, knowledge and expertise are available to all parties involved, allowing for the constant transformation of activities by engaging tourists in actively co-creating their experiences. Significant beneficiaries, such as visitors, service providers, and destination marketing organizations, participate in the smart tourism ecosystem’s combination of systems, structures, and technology to co-create value and experience its advantages. The application of neuroscience in smart tourism ecosystem can help to better understand the needs and expectations of tourists, to design more efficient and sustainable services, and to measure the impact of tourism on society and the environment. Sustainable value co-creation based on neuroscientific approach are the new building blocks of smart tourist ecosystems to attain visitor satisfaction and loyalty by establishing positive associations with the co-creation of tourist experiences. Considering neuroscience as a valuable tool for understanding how tourists interact with their environments and how ICTs can be used to enhance their experiences, this paper analyzed literature on smart tourism ecosystem and sustainable value co-creation to provide insights into how sustainable smart tourism can be improved through the use of the neuroscientific approach.