In this article we evaluate the determinants of the Employment in Innovative Enterprises in Europe. We use data from the European Innovation Scoreboard of the European Commission for 36 countries in the period 2000-2019 with Panel Data with Fixed Effects, Panel Data with Random Effects, Dynamic Panel, WLS and Pooled OLS. We found that the “Employment in Innovative Enterprises in Europe” is positively associated with “Broadband Penetration in Europe”, “Foreign Controlled Enterprises Share of Value Added”, “Innovation Index”, “Medium and High-Tech Product Exports” and negatively associated to “Basic School Entrepreneurial Education and Training”, “International Co-Publications”, and “Marketing or Organizational Innovators”. Secondly, we perform a cluster analysis with the k-Means algorithm optimized with the Silhouette Coefficient and we found the presence of four different clusters. Finally, we perform a comparison among eight different machine learning algorithms to predict the level of “Employment in Innovative Enterprises” in Europe and we found that the Linear Regression is the best predictor.