The challenge of countering the conflicts and managing the crises created by Iranian meddling in regional countries such as Syria, Iraq, Yemen, Lebanon and some Gulf nations, has pushed the US President Donald Trump’s administration and its regional strategic allies to reconsider their policies and strategies with regard to dealing with Iranian expansionism. Iran has undermined regional peace and security as well as contributing to the collapse of nation-states and the proliferation of terror groups in the region. Therefore, the Arab Gulf countries and the US administration aim to form a military and political alliance (an Arab NATO) known as the Middle East Strategic Alliance (MESA). The alliance aims to stand up to Iranian intervention in the Arab region. It would be part of the US administration’s attempts to besiege the Iranian state in addition to its economic sanctions and political pressures aimed at changing Iranian behavior. Therefore, in the following analysis, we will detail the aims of the alliance, the phases of its evolution, its challenges, especially from the Iranian and Israeli point of view, its chances of success and its future prospects in light of the current complicated circumstances in the Middle East.