The chapter presents a spatial interaction entropy model that addresses the dynamics of urban growth using sites from the Late Uruk period in southern Mesopotamia as examples. Modelling presented addresses to what extent geography, transportation, and factors that make locations attractive for trade and settlement affect why some settlements grow while others stabilize or diminish in size through time. The results show that geographic and transport factors can enable some regions, such as the northern alluvium in southern Mesopotamia, to have some initially favourable advantages for urban growth. In contrast, greater attraction to specific centres and decreasing mobility of goods and people to many towns enable sites such as Uruk to rapidly grow through positive feedback effects without natural population increase. This growth also influences other settlements’ populations and use of the transport infrastructure, where aggregation of population to few centres leads to a large number of small sites or even near abandonment of sites. Other results explore how external trade and contacts affect urban growth. Overall, the results demonstrate a quantitative model that is useful in explaining periods of rapid urban growth and regional urban layout transformations without necessarily having full knowledge of the archaeological data.