Based on most recent statistics published by the European Parliament and the Organization for Economic Cooperation and Development (OECD), the Romanian and Czech Republic business environment need more support from the European Union (EU) and the policymakers since the outcomes are lagging behind those belonging to other EU Member States and other higher income countries. The paper tackles the results of a content analysis of the Global Innovative Index 2013 to 2022 across all pillars for Romania and the Czech Republic. The findings are highly important since they provide a basis for quantitative research on the framework conditions for innovative and sustainable entrepreneurship in the two countries, as follows: (a) regarding Czech Republic, data indicates that there is a positive association between background/education level and innovation, while, this situation specific to Czech Republic is not reflected in a higher score, which is comparable to Romania; (b) despite this, Romania demonstrates a stronger performance with respect to the selected indicators. All in all, on the one hand, the analysis suggests that the effect of education or access to information and communication technology (ICT) on business activity is not significant, which is evidenced by Romania’s lower score and stronger business activity and, on the other hand, the results display the answer for research question that Business Sophistication Index and the Knowledge and Technology Outputs Index has an influence on sustainable business and possibility to develop innovative business ideas and these topics have to be connected with planned research.