This paper highlights a spatial interaction entropy maximization (SIEM) model to reproduce and understand past human settlement hierarchy in Central Anatolia (CA) and the Khabur Triangle (KT) during the Middle Bronze Age (ca. 2000–1600 BC). We propose applying SIEM to understand which sites and areas would have become prominent in this period by using known archaeological sites as point data and textual evidence for calibration purposes. The model addresses to which extent general factors such as topography, transportation, or social–ecological advantages (e.g., environmental benefits, external contacts, religion) make locations attractive for trade and settlement and why some archaeological sites become more prominent than others in the period discussed. The modelling results have been checked against the observed data from archaeological survey carried out in the KT and CA in order to explain the best fits. The results show that geography and topography can explain the growth of some main urban centres. In other cases, settlement hierarchies are generally explained by different initial advantages (endogenous or exogenous) for each site. Similar patterns are evident in CA and the KT, where movement constraint is due to political landscapes fragmented into numerous competing polities. In the KT, movement is slightly more restricted than CA, suggesting that warfare intensity is higher in open plains than in hilly and mountainous landscapes. Furthermore, SIEM is demonstrated to be useful in characterizing areas of interactions on different spatial scales in CA and the KT. Overall, the results demonstrate the advantage of SIEM model to enable researchers to account for missing empirical data, to compare settlement and interaction dynamics in different regions and to explain which underlying factors are beyond the reproducible observed patterns.