Today, the realization that certain economic units, such as universities or other large tertiary educational institutions have an impact on the economy of their region has gained prominence. There is a growing demand for precise studies on the economic impact of such entities, and the issue has attracted considerable attention in the scientific community. The examination of their economic impact is especially interesting when we compare regions with different levels of development, characterized by a successful international university. The different methods used in the literature render comparisons difficult; therefore, our focus is to recommend a method for investigating universities in different countries. In the absence of regional input-output matrices, a multiplier based approach is suggested for the first and second mission (education and research), while the application of a set of indicators is recommended for the third mission (knowledge transfer-related). There are several substantial problems in assessing the economic impact of universities. First, the definition of impact; second, measuring and estimating first-round expenditures and avoiding double-counting; third, estimating the model parameters (e.g. multipliers); fourth, the quantification of third mission activities. In this paper, we clarify theoretical definitions, resolve some contradictions, and consequently, recommend a feasible method considering the circumstances in Hungary.