The historic meeting will see Charles hold a private audience with the Pope during the Rome leg of their Spring trip.
With Italy marking its jubilee year, the visit of King Charles will signify a major sign of intent on the monarch's behalf.
Millions of visitors are set to descend on the Italian capital's ancient streets to celebrate the jubilee events which only take place every quarter of a century.
Charles will be the first monarch in a decade to meet with the leader of the Catholic Church.
It is thought that the King has been keen to meet Pope Francis in recent times, with the Pontiff now 88-years-old and having suffered from ill health and mobility problems over the last number of years.
According to the Mirror, Charles is also set to visit various Vatican landmarks such as the Sistine Chapel.
The small 15th century church is known the world over for its frescoe-covered ceilings, the work of famed Renaissance painter Michelangelo.
Charles and Pope Francis have met on two other other occasions, most recently in 2019 when the then Prince of Wales visited the Vatican.
That trip was to attend the canonisation of Cardinal John Henry Newman, the first English person to be named a saint in decades.
Their other previous encounter came back in 2017 when Charles and Camilla visited Rome.
The King has of course also met with previous Popes such as John Paul II in 1985 and Benedict XVI in 2009.
In a remarkable twist, Charles and Camilla also postponed their wedding in 2005 so they could travel to the funeral of John Paul II.
The gesture and effort made by the Royal family was not lost on those within the Vatican, with the papacy remarking on the closeness between faiths that it demonstrated.
Queen Elizabeth II was the last monarch to meet with Pope Francis back in 2014 when she had a personal audience with him in Rome.
However, due to his own poor health, the Pontiff was unable to travel to London for the Queen's funeral in 2022.
Charles, who is continuing treatment for cancer, remains set on returning to a full Royal schedule, both domestically and internationally.
Having been diagnosed in February last year, Charles has so far managed to fulfil his duties despite requiring weekly treatment in London.
In one of his first official acts of the New Year, the King will host three organisations dedicated to educating future generations on the horrors of the Holocaust on Monday.
He
is also set to travel to Poland for the 80th commemoration of the
liberation of Auschwitz concentration camp later this month.