The same disease agent, Yersinia Pestis, which instigated the Justinian Plague and the Black Death, caused the Shiruyah plague in the Persian Empire in 628 CE. However since the Roman-Persian wars, Persian civil wars, and the 7th century Arab conquest have been the main focus of the historians, the study of the Bubonic plague as one of the most influential contributors to the transformations of the 7th century Middle East has been neglected. The climate of the western Iranian provinces, particularly Mesopotamia and Khuzstan, provided the disease agent with the optimum environment for its survival, multiplication, and spread. The impact of Shiruyah plague must have been similar to that of the three other well-known incidents of the pestilence in the history. Moreover, immediately following the plague, the area now referred to as the Middle East went through massive transformations after a demographic decline. In this study I direct to the question of the reason behind the lack of focus on the Shiruyah plague as equally significant in historiography as the Justinian plague, Black Death, (and in some extent that of the 19th century in China). My aim is to find out if the plague can be regarded as one of the main factors responsible for the transformation of the Middle East in the 7th century CE? In this presentation I use an interdisciplinary method for conducting research. The most recent scientific findings like Boone (2009) and Bosworth (2010) and the works of the archaeologists like Drancourt (2006) and Adams (1965) are foundation for finding the cause of the disease and for assessing whether the Iranian western provinces were able to provide an appropriate milieu for the agent to trigger a pandemic. The textual sources like the Muslim accounts by Bal’ami, Dinawari, Mas??d?, Maskawayh, Tabar?, Tha’alibi as well as Roman-Byzantian accounts by Procopius, Agathias, Sebeos, Menander the Gurdsman, Theophphylact Simocatta, Zuqnin, Socrates Scholasticus, John Malalas, and Theophanes, enhance and supplement the scientific and archaeological findings on which I draw for arriving at my conclusions.