This article examines the impact of the macroenvironment on enterprises in euro-area countries over the period 2006–2020. Our study builds on important works and theories in the field of business, including the work of Kar and Özsahin. We employ the Panel Least Squares method to estimate the coefficient of selected variables. We identify political, institutional (government effectiveness index, regulatory quality index, rule of law, market capitalization of company, control of corruption, political stability and absence of violence) and financial (financial development index, gross domestic product, inflation rate, unemployment rate, public debt) determinants that can have an effect on entrepreneurship. The article aims to fill a gap in the existing literature by providing new insights from the Eurozone and updated data that were not included in previous literature reviews and studies. In this way, we contribute to expanding knowledge about the relationship between macroeconomic factors and entrepreneurial activities in this specific geographical area, considering the lack of current analyses. According to our results, there is a positive statistically significant relationship between entrepreneurship and gross domestic product per capita, regulatory quality index, and market capitalization of the company and a negative statistically significant relationship between entrepreneurship and rule of law, and public debt.