The Sistan region has played a prominent role in establishing and expanding civilization in the eastern region of Iran in different historical periods. The region’s favorable environmental conditions, including abundant water, fertile soil, and diverse flora and fauna, attracted various ethnic groups to settle and achieve significant advancements by constructing numerous cities and settlements. Over its documented existence, Sistan with a rich collection of historic buildings and archeological sites has experienced three periods of extensive settlement and three periods of non-settlement, commonly referred to as gap periods. Multiple factors have contributed to the development of Sistan socially and settlement wise. This article aims to identify the influential factors in the cycle of formation and collapse of civilizations in Sistan by examining geographical, historical, and archaeological factors. Among these, water availability, political considerations, and other natural and human-related aspects stand out as the main contributors to this cyclic pattern.