With the emphasis on cross-industry cooperation and the increasing complexity of the consumer market, an open and innovative business ecosystem has become a trend, and companies are no longer competing on their own, but rather between systems and systems. This study explores the development of SME cluster operations from a business ecosystem perspective. It summarizes the influencing dimensions and relevant factors of SME cluster ecosystem operation through literature research and expert interviews. We utilize the Fuzzy DEMATEL method and Interpretive Structural Model and classified by classification of matrix multiplication method. At the same time, this study figures out the factors’ correlation and characteristics and further develops their management implications to provide a reference for enterprises and subsequent research. The results reveal that robustness and niche creation with significant influence and low dependence are considered critical factors to influence other factors. Therefore, decision-makers should consider prioritizing control over factors in this category.