Although ISIS succeeded in capturing parts of Iraq and Syria between 2012 and 2016, it never achieved international acceptance, and its rulers' behavior was in conflict with the principles and rules of the United Nations. However, the international rejection of ISIS does not mean ignoring the role of this group in regional relations. In recent years, there have been widespread developments in the Middle East, including the fall of Bashar al-Assad's government in Syria, the escalation of tensions between Hamas and Israel, and geopolitical changes that have affected the relations of countries in the region. These developments have made it more obvious than ever before that there is a need to review the models for confronting terrorist groups such as ISIS. This study aims to examine the impact of geopolitical indicators of confronting ISIS on the regional relations of the Islamic Republic of Iran. In this regard, a mixed research method (qualitative-quantitative) has been used. In the qualitative section, data were collected and coded using the opinions of experts and specialists in the field of Takfiri groups and ISIS. In the quantitative section, a researcher-made questionnaire was designed based on the findings of the qualitative section and completed by experts and planners of international relations in the Revolutionary Guard Corps. The research findings show that the impact of ISIS on the regional relations of the Islamic Republic of Iran is influenced by historical backgrounds, socio-cultural axes, security policies, and geopolitical factors. Also, recent regional developments, including the fall of Assad and the war between Hamas and Israel, have had an impact on the extent and manner of ISIS’s impact on regional relations. By examining geopolitical factors, this study suggests solutions to counter the negative effects of ISIS on Iran’s regional relations. The research findings show that the impact of ISIS on the regional relations of the Islamic Republic of Iran is influenced by geopolitical factors. Also, recent regional developments, including the fall of Assad and the Hamas-Israeli war, have affected the extent and manner of ISIS's influence on regional relations. This study also suggests strategies to counter ISIS's negative effects on Iran's regional relations.