The nexus of innovation, entrepreneurship and competiveness represents a real challenge for the European economy, and not only, taking into account the important role of these determinants of inclusive and sustainable development in the context of the Fourth Industrial Revolution. The aim of this article is to explore the relation between innovation, entrepreneurship and national competitiveness, at the EU level, in order to highlight how innovation and entrepreneurship can influence the level of competitiveness and inclusive development in these countries. The results of the comparative analysis based on means-testing using independent samples t-test, at EU level, show that there are significant differences between low-medium innovation performance countries group and high and very high innovation countries performance group in terms of competitiveness, innovative entrepreneurship, productive entrepreneurship and economic and inclusive development, fact which emphasizes the need to take specific actions to improve EU innovation performance, especially in the EU countries included in the low-medium innovation performance countries group for improving national competitiveness and implicitly increasing the level of development. The correlation and regression analysis results suggest that the high level of national competitiveness in some EU countries can be mainly explained by high level of innovation performance, high level of innovative and productive entrepreneurship. The findings of the study can be useful for policymakers to formulate policies for improving national competitiveness within an inclusive development.