The European Union is a unique economic and political union, a single "internal" market with over than 510 million inhabitants. Further coordination in the field of taxation is required, since it is not yet integrated into the E.U. policy and remains under the responsibility of national governments. However, the economic and financial turmoil caused by the crisis of 2008 and the new challenges resulted from the globalization and digitalization of the economy, require profound reforms to tax systems. Thus, fiscal policy is a significant priority on the EU agenda: firstly, in order to stabilize public finances, stimulate growth and competitiveness and finance the European social welfare model as well as to tackle tax evasion and aggressive tax planning, developed mainly by multinationals. The present paper attempts to explore on a theoretical and empirical basis the challenges and possible developments towards harmonization in European taxation, at a critical juncture, not only for the integration but also for the existence of the European Union. More specifically, it investigates the Greek taxation and its structural weaknesses through empirical research conducted with questionnaires distributed among 225 tax officers, accountants, and accounting executives and statistical processing of their response. The results were examined through descriptive analysis, segmented in seven theoretical domains based on the examination of both audit literature and the present taxation state of Greece. The findings reveal that structural problems remain unresolved within the Greek tax system. However, it is understood that issues of distrust toward the taxation system may hinder harmonization processes.