Taoiseach Micheál Martin will meet Pope Leo XIV for the first time at the Vatican while on a trip to Italy.
They are expected to discuss the crisis in the Middle East, including attacks against Christians in the West Bank and Jerusalem.
The Taoiseach will meet Italian Prime Minister Giorgia Meloni after his visit to the Vatican.
Mr Martin is expected to outline Ireland’s priorities in the upcoming Presidency of the EU, which gets under way on 1 July.
Pope Leo was inaugurated just over a year ago, the first US pontiff, and a spiritual leader seen as combining the social justice instincts of his predecessor Pope Francis, with some of the more conservative priorities of the late Pope Benedict XVI.
In recent months, he has become distinctly outspoken about what he has condemned as the current zeal for war.
Although he has not mentioned US President Donald Trump by name, Mr Trump has angrily hit out at the Pope for apparently criticising US foreign policy.
Mr Martin and Pope Leo are expected to have much to discuss, following the events surrounding the Israeli interception of the Gaza aid flotilla, and US-Israel war on Iran.
Mr Martin will also have a bilateral meeting with Holy See Cardinal Secretary of State, Pietro Parolin.
Following the Vatican meetings, the Taoiseach will visit the Pontifical Irish College in Rome to meet members of the college community and view its archives.