The main goal of this article is evaluation of some challenges that resulted in creating some obstacles before regional trade blocs in the Middle East. In recent years, regionalism in light of geographical and geopolitics relations have influenced interdependence and common interests. Hence, states have tended to cooperate and organize interaction in some issues such as political, economic, and cultural context. This article, with emphasis on Middle East and promotion of cooperation and security space mitigation, pursues to answer the question that what has challenged regional trade blocs in the Middle East. With descriptive-explanative method, this article argues some political factors such as structural contrasts and competitions among the Middle Eastern countries, internal crisis in regional countries and influence of intra-regional actors and multiple economic factors such as underdevelopment in difference levels, rentier states and weakness of privatization are more important factors that influenced free trade blocs in the Middle East.