It's the leaders first trip abroad since the agreement with the EU and US.
He'll take a 120-strong delegation of Iranian business people to Paris and Rome for a five day trip.
Pope Francis will welcome the Muslim president to the Vatican before he meets the Italian prime minister.
The Holy Father has been keen to repair damaged relationships between the Catholic Church and Islam and is expected to bring up interfaith dialogue.
After sanctions were lifted on Iran, following the deal, Francis said it was "a definitive step toward a more secure and fraternal world".
It's possible the Pope could raise Syria at the meeting.
Iran is a strong ally of embattled President Assad.