Economic complexity is a modern indicator for assessing countries’ productive and technological capabilities, focusing on the quality and diversity of goods and services. This index has a direct relationship with sustainable economic growth and global competitiveness. Economies with higher complexity are more capable of producing advanced, knowledge-based products and demonstrate greater resilience to economic shocks. Among the key determinants of increased economic complexity is domestic R&D accumulation, which strengthens the foundations of a knowledge-based economy. This factor not only fosters the creation of new knowledge but also facilitates the localization and utilization of global technological achievements, thereby contributing to the formation of sustainable competitive advantages. When combined with economic freedom, domestic R&D accumulation enhances knowledge productivity and accelerates the development of a knowledge-driven economic system by facilitating the exchange of knowledge between public and private sectors and expanding international cooperation. This study examines the interactive effect of domestic R&D accumulation and economic freedom, along with the roles of information and communication technology (ICT) and education and human capital, on the economic complexity of selected science-producing countries-divided into two groups: developed and developing economies-over the period 2003–2021, using the random effects method. The results reveal that, in both groups of countries, the interactive effect of domestic R&D accumulation and economic freedom is positive and statistically significant. Moreover, the education and human capital index is positive and significant in developed countries but negative and significant in developing ones. In addition, the ICT index shows a positive and significant impact in developed countries, while in developing countries, its effect is negative and statistically insignificant