Despite sustainable wine tourism being one of the hottest topics of the moment, there is still a considerable knowledge gap. If managed with due care and consideration of the region’s carrying capacity, wine tourism can be an essential regional development tool for improving business performance, environmental awareness, and community values. On the other hand, it can be responsible for negative environmental impacts, creating local resentment. This paper explored and contextualized wine tourism and sustainable winegrowing practices in the Portuguese Douro wine region. The aim was to offer practical recommendations and directives for such a unique landscape. From the adoption of regenerative agriculture and natural-based solutions at the field level to engaging in sustainability wine programs or certification schemes integrating both sectors, it is indispensable to develop frameworks to assess sustainability performance, tourism development, and the impact on the local population. Nevertheless, to accomplish business success and territorial development, a win–win relationship between all stakeholders is foremost needed. The Douro region must therefore start by investing in stronger collaboration networks between local actors through careful and integrated planning so that the needs of all interested parties, including its residents, are considered and incorporated in future sustainable tourism initiatives.