The aim of a significant part of current wine technology research is to better understand and monitor mixed culture fermentations and optimize the microbiological processes and characteristics of the final wine. In this context, the yeast couple formed by Lachancea thermotolerans and Saccharomyces cerevisiae is of particular interest. The diverse results observed in the literature have shown that wine characteristics are dependent on both interactions between yeasts and environmental and fermentation parameters. Here, we took a multiparametric approach to study the impact of fermentation parameters on three different but related aspects of wine fermentation: population dynamics, fermentation, and volatile compound production. An experimental design was used to assess the effects of four independent factors (temperature, oxygenation, nitrogen content, inoculum ratio) on variables representing these three aspects. Temperature and, to a lesser extent, oxygenation and the inoculum ratio, were shown to constitute key factors in optimizing the presence of Lachancea thermotolerans during fermentation. The inoculum ratio also appeared to greatly impact lactic acid production, while the quantity of nitrogen seemed to be involved more in the management of aroma compound production. These results showed that a global approach to mixed fermentations is not only pertinent, but also constitutes an important tool for controlling them.