Wine fermentation is a specific and complex research subject and its control is essential to ensure full process completion while improving wine quality. It displays several specificities, in particular, (i) musts with a very high sugar content, low pH, and some limiting nutrients, as well as a great variability in must composition according to the year, grape variety, and so on; (ii) atypical fermentation conditions with non-isothermal temperature profiles, a quasi-anaerobiosis and legal constraints with a limited and predefined list of authorized operations. New challenges have emerged, related to the increasing diversity of commercially available yeast strains; the fluctuating composition of musts, particularly owing to climate change; and sustainability, which has become a key issue. This paper synthesizes approaches implemented to address all these issues. It details the example of our laboratory that, for many years, has been developing an integrated approach to study yeast diversity, understand their metabolism, and develop new fermentation control strategies. This approach requires the development of specific fermentation devices to study yeast metabolism in a controlled environment that mimics practical conditions and to develop original fermentation control strategies. All these tools are described here, together with their role in the overall scientific strategy and complementary approaches in the literature.