It will be Mr Putin’s second meeting with Pope Francis, and the latest episode in a long-running but sometimes fraught relationship between the Kremlin and the Vatican.
At Wednesday’s meeting, the president of Russia and the Bishop of Rome will cover “specific international problems, in particular the situation in Ukraine with emphasis on inter-religious relations and the activities of the Ukrainian Greek Catholics,” Kremlin spokesman Yuri Ushakov told reporters on Tuesday.
Russian leaders traditionally visit the Pope during any visit to Italy, and Russian and Soviet leaders have maintained links with the Vatican since formal contacts were established between the Holy See and the Kremlin under Mikhail Gorbachev.
For the Kremlin, these meetings are an important source of "supplementary external legitimacy," said Andrei Zolotov, a Russian journalist who specialises in religious affairs.
"That is particularly important for Moscow in the present political situation."
At their last meeting in November 2013 the notoriously tardy Mr Putin kept the Pope and his aides waiting for nearly an hour (the Kremlin blamed the delay on protesters outside Mr Putin’s Rome hotel).
Mr Putin’s team hailed that meeting as a success, and it raised hopes of a rapprochement between the Catholic and Russian Orthodox Church hierarchy.
But analysts say a mooted historic meeting between the Pope and Patriarch Kirill, the head of the Russian Orthodox Church, is now off the cards - largely thanks to the war in Ukraine.
To date Pope Francis has avoided taking a strong line on the Ukraine crisis, confining himself to expression of dismay at a “war between Christians” and implicitly – but not specifically - condemning the annexation of Crimea by calling for respect for international law.
According to one leading Vatican analyst, the Russians have taken care to express their appreciation for that restraint.
Writing in Rome’s Corriere della Sera newspaper on Tuesday, Massimo Franco said that in the past few days Patriarch Ilarione of the Russian Orthodox Church had “discreetly” reaffirmed gratitude for the Vatican’s “independent” line.
That is partly because the Vatican is sees Mr Putin’s Kremlin as an ally in other areas.
Apart from a joint commitment to “traditional values” – most prominently in opposition to gay marriage – the Third and First Romes have shared interests in the Middle East.
Pope Francis has also been outspoken in his condemnation of persecution of Christian minorities in the Middle East, blaming the fanaticism of groups like the Islamic State in Iraq and the Levant (Isil) for driving Christians from their homes.
The Vatican openly opposed Western countries entering the war in Syria, and some analysts suggest that the “moral pressure” of a vigil for peace led by Pope Francis in September 2013 was instrumental in averting airstrikes.
In turn, Mr Putin has sought to reassert Russia’s traditional claim to be the protector of Christians in the Middle East, and has long portrayed his ally Bashar Assad, the Syrian president, as a secular protector of religious minorities against violent Islamism.
Russian weapons deliveries and diplomatic cover at the United Nations have been crucial to Mr Assad’s survival since an uprising against his rule in 2011 broke into a full-blown civil war.
For the Vatican, that makes Mr Putin an “unavoidable and valuable interlocutor for containing Islamic terrorism,” said Mr Franco.
But Pope Francis is coming under increasing pressure from leaders of the Ukrainian Greek Catholic Church to take a more forceful line.
Sviatoslav Shevchuk, the Archbishop of Kiev Halych and the head of the Ukrainian church, has openly criticised the Vatican’s “ambivalence” over Russia’s role in the war.
“We understand Rome is trying to safeguard its ties with Moscow, but we also know Christ has always been on the side of those who suffer. In this conflict, it is Ukraine which is suffering – and the Holy See, whose diplomacy is service of the Gospel, should be at our side,” he said in May in an interview with La Croix, a French Catholic daily.
Most combatants on either side of the war in Ukraine are eastern Orthodox.
But the Ukrainian Greek Catholic Church has been outspoken in its support of Kiev, and some fighters, especially on the pro-Russian side, see the war as a continuation of centuries of enmity between Orthodox Slavic civilization and the Catholic dominated West.
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