The trip – a formal state visit between the world's two smallest countries – is actually no small matter.
Monaco's motto is "Deo Juvante" (With God's Help) and the historical alliance between Monaco (whose state religion is Catholicism) and the Vatican trace back centuries.
Considerable political, sociological and cultural ties exist between the two nations and these have become even more pronounced and important since the arrival of Princess Charlene.
"Charlene has embraced the Catholic religion and is inspired by it," a Monaco observer tells PEOPLE. "She is devoted to it and impressive in her fidelity."
And there's more than symbolism involved in the fact that Charlene's first state visit since the birth of her twins in December 2014 is to a nation even smaller than Monaco, which represents over one billion Roman Catholics.
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"Catholicism is the state religion [in Monaco]. But for me, it represents much more. The values of this religion profoundly touch me and correspond perfectly to my spirit
"In January 2013, Prince Albert took me to the Vatican to present me to Pope Benedict XVI, just as Prince Rainier did with Grace Kelly and Pius XII," she recalled, adding, "that experience was extremely intense and moving for me."
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Just weeks later, the royal couple cut short a March visit to Palau in the South Pacific to attend the inaugural mass of Pope Francis. They both took communion from His Holiness on this occasion.
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Indeed, after her children's premature birth, her first authorized exit from the maternity ward at Princess Grace Hospital was to attend chapel mass. "I prayed, as always, for everyone," she told Paris-Match afterwards, "but I especially thanked the Lord. I have such luck, a happy husband, two children in good shape."
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And in a year of relatively few public appearances, she reemerged last November to speak at the Vatican on behalf of her foundation.
Charlene often attends mass discreetly with her husband (and recently with their children) at one of Monaco's five Roman Catholic churches. She also openly confides special appreciation for the peace of the country's Notre-Dame-Immaculate Cathedral, going there often privately to lay flowers for Prince Rainier, Albert's late father.
Charlene, a veteran Monaco observer says, "enjoys going to church. She likes it. In a sense, you feel that it provides a spiritual balance, that contrast to her life as a princess, which she seeks."
Albert, who has applauded Pope Francis' call for environmental responsibility, will be discussing and sharing some organic farming tips during next week's visit.
Sources tell PEOPLE that the prince will be bringing photographs and information concerning the techniques used at his 125-acre working farm, Roc Agel, which Francis is interested in implementing at the papal retreat, Castel Gandolfo.