Since the end of the Cold War, most wars have taken place either in the Middle East or the adjacent South Asian region. Unfortunately, all of these wars and conflicts were between Unequal Military Powers (UMPs), and therefore the result was obvious. The infrastructure and the social fabric of Iraq, Libya, Syria, Yemen, and Afghanistan have been destroyed, and hundreds of thousands of innocent people were killed, while millions have been rendered homeless and forced to leave their homes to take refuge in foreign lands. Iran, on the other hand, remains under US sanctions due to its nuclear programme, which not only concerns the extra-regional powers but also the regional states. Saudi Arabia has repeatedly voiced its concerns about increased nuclear activities by Iran, which threatens regional security. Saudi officials have stated that “Iran’s moves to produce uranium enriched to 60 per cent fissile purity and uranium metal to 20 per cent ‘represent an increasing threat’ to regional security and non-proliferation of weapons.” According to a recently published International Atomic Energy Agency (IAEA) report on Iran, the country is producing more Uranium metal in violation of its commitment under the Joint Comprehensive Plan of Action (JCPOA). Therefore, it hampers efforts to secure “a comprehensive nuclear deal that ensures global and regional security and stability.” The situation in the region, Middle East, and South Asia (MESA) call for a comprehensive intra-regional dialogue, perhaps at the Summit level. Perhaps, the US Administration is taking revenge for its military defeat from the Taliban government without any consideration for the plight of the people of Afghanistan. Afghanistan remains under the clouds of uncertainty despite the complete withdrawal of foreign forces. The US signed a Peace Agreement with the Taliban in Doha on February 29, 2020, under which all its forces were supposed to withdraw from Afghanistan in 14 months. However, President Biden sought a little more time to complete the process, and finally, all US and NATO troops left Afghanistan by the middle of August, and the Taliban entered Kabul without firing a shot on August 15, 2021. Though it is not an unexpected outcome, it has taken a little more than expected for regional as well as extra-regional countries to recognize the new Afghan government led by the Taliban. Now, this is unfair with the people of Afghanistan who have already suffered immensely due to repeated foreign occupations and continued wars and conflicts over the last four decades. Because the US leadership should have visualized that the Taliban would ultimately take over Afghanistan after US and NATO troops have left the country they had controlled by force only. The people of Afghanistan are starving due to a lack of basic amenities, which are not available to them due to a lack of requisite resources. Despite Pakistan’s best efforts to provide humanitarian assistance in the form of food and medicines, Afghans are going through a torrid time due to extremely harsh weather and a lack of international support at this critical time. The new Taliban government does not have enough resources to manage the state affairs due to US restrictions on the release of funds necessary to provide relief to the people of Afghanistan. Perhaps, the US Administration is taking revenge for its military defeat from the Taliban government without any consideration for the plight of the people of Afghanistan for which the US cannot be absolved under any pretext. Moving to the Middle East, the Yemen war has entered into its eighth year. Yemen, like Syria, is a classic example of a civil war turning into a larger regional conflict. Without going into the history of Yemen’s civil war, the ongoing military conflict started in 2014 when KSA-led regional forces intervened to reinstall the government of Abdrabbuh Mansour Hadi who had fled out of Yemen due to resurgent Houthi’s advances on the Capital Sana. Although the Saudi-led offensive achieved its primary objective of restoring Hadi’s government, the conflict developed into full-scale war. The people of Yemen now face famine and large-scale internal displacement and the end of the crisis is not in sight. Houthis have been carrying out missiles and rocket attacks on Saudi oil facilities regularly but on January 17, they claim to have carried out a drone strike against oil facilities near Abu Dhabi. Not surprisingly, the UAE has pledged to retaliate in kind. While Libya remains unstable, there is no respite to the Syrians also. Growing out of the consequences of Arab Spring in early 2011, the Syrian conflict has had a much wider impact on regional security. The number of regional and extra-regional states and non-state actors involved in the Syrian conflict perhaps outnumbers all other regional conflicts including Libya, Yemen, and even Afghanistan. That is why the Syrian conflict remains unresolved even after continued fighting for over a decade now. The challenges to regional security in MESA are serious and need to be looked into at the Summit level. The regional stakeholders must take charge before the extra-regional forces intervene again militarily, while their political intervention cannot be blocked due to their long-term interest in the region. The writer is the author of the book ‘Nuclear Deterrence and Conflict Management Between India and Pakistan’. He is presently working as the Director of the Centre for Aerospace and Security Studies (CASS).