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The application of starter is a common practice to accelerate and steer pomegranate wine fermentation process. However, the use of starter needs to better understand the effect of the interaction between starter and native microorganisms during alcoholic fermentation. In this study, high-throughput sequencing combined with metabolite analysis were applied to analyze the effect of commercial Saccharomyces cerevisiae inoculation on the native fungal community interaction and metabolism during pomegranate wine fermentation. Results showed there were diverse native fungi in pomegranate juice, including Hanseniaspora uvarum, H. valbyensis, S. cerevisiae, Pichia terricola and Candida diversa. Based on ecological network analysis, we found S. cerevisiae inoculation transformed the negative correlations into positive correlations among the native fungal communities, and decreased the Granger causalities between native yeasts and volatile organic compounds. This might lead to the decreased contents of isobutanol, isoamylol, octanoic acid, decanoic acid, ethyl laurate, ethyl acetate, ethyl hexadecanoate, phenethyl acetate and 2-phenylethanol during fermentation. This study combined correlation and causality analysis to gain a more integrated understanding of microbial interaction and the fermentation process. It provided a new strategy to predict certain behaviors between inoculated and selected microorganisms and those coming directly from the fruit. IMPORTANCE Microbial interactions play an important role in flavor metabolism during traditional foods and beverages fermentation. However, we understand little about how selected starters influence the interactions among native microorganisms. In this study, we found S. cerevisiae inoculation changed the interactions and the metabolisms of the native fungal communities during pomegranate wine fermentation. This study suggest that the starters inoculation should take into account not only the positive features of starters, but also to characterize the microbial interactions established among the starters and native communities. It may be helpful to select the appropriate starter cultures for winemakers to design different styles of wine.