The commercial prosperity and growth of handicraft industries during the Seljuk period in Iran and Rome, and the recognition of the importance of roads in facilitating trade and increasing wealth, led to the establishment and construction of roads. Although the extent of trade in Seljuk Iran was widespread, Eastern Rome (Anatolia) played a significant role in trade through land and sea routes with Iran. Which trade routes are recognizable in the Seljuk territories of Rome and Iran, and which routes were more important during the Seljuk period between these two lands are among the questions raised in this research. The main goal of this article is to recognize the trade routes of transportation between Seljuk Iran and Rome in the fifth and sixth centuries AH based on archaeological evidence and historical written sources. Understanding the cultural interactions, structural characteristics, and architectural styles of caravanserais in these two lands, and identifying their differences and similarities, is another objective. This research was conducted using library and field methods with a historical and archaeological approach. The variables of this research are the East-West international trade routes and Seljuk caravanserais in Iran (15 caravanserais) and Anatolia (17 caravanserais). As a result, several important trade routes between Iran and Anatolia in the Seljuk period were identified. Among them, the Tabriz-Konya route was the main commercial communication route between these two lands. The caravanserais established are mainly located on the Great Khorasan Road. The examination of the architecture of the caravanserais showed that although the Seljuk caravanserais in Iran and Anatolia have similar uses, they are generally different in terms of style and plan, and the roots of the Seljuk caravanserais cannot be traced back to Iran.