Shimon Peres and Mahmoud Abbas will travel to the Holy See after the pontiff extended an invitation during his visit to the region last month.
They'll be joined by several Christian leaders from the region, with some suggesting Patriarch Bartholomew, the most senior leader among the Orthodox Church, will also be there.
No details have been announced of the format or the exact location of the meeting but some reports say it will take place behind closed doors either in the papal residence or the Vatican gardens.
Church officials have made it clear the meeting will be one of prayer and not politics and during a briefing with reporters on his way back from the Holy Land, Pope Francis said: "This prayer meeting will not be for mediation or to find solutions.
"We are just meeting up to pray. Then everyone goes home."
Dr Harry Hagopian is an international lawyer and church consultant.
Speaking to Premier's News Hour he explained how he sees this meeting going.
Despite the statements from the Church, many commentators have suggested this could be what's needed to kick start peace negotiations.
Talks broke down earlier this year and there's been no high-level meeting for 12 months.
There's concern that with a change of leadership in Israel and Palestine coming soon, negotiations could be put back further.
Dr Hagopian told Premier's News Hour time is running out for the current Presidents.
During Pope Francis' visit to the region he won praise for managing to speak in support of both sides.
Although church leaders have previously helped in the peace process, a meeting of this kind has never taken place before.