Donald Trump will meet Pope Francis for the first time on Wednesday (local time), in an encounter that will take place at the Vatican.
They may both be leaders of global stature, but their personalities could hardly be more different.
While the meeting is likely to be cordial, it comes against a backdrop of tension and public disagreement on a range of issues.
Climate change and the environment
President Trump has threatened to pull the US out of the 2015 Paris accord on reducing greenhouse global gas emissions, and in March signed an executive order dismantling environmental regulations enacted under Barack Obama.
Pope Francis, in stark contrast, has called for concerted action to halt global warming and a shift away from the use of fossil fuels.
The Pope is expected to give the President an English copy of his encyclical on the environment, "Laudato Si" (Praise Be) - a pointed reminder of his belief that climate change is largely man-made and needs to be urgently addressed.
Refugees and migrants
The Pope has repeatedly called for compassion to be shown to refugees and migrants and is himself the product of an Italian family that migrated to Argentina.
President Trump, in contrast, attempted to ban the entry of Syrian refugees in January, halted the issuing of visas to people from several Muslim countries, and wants to build a wall along the Mexican border.
The Pope criticised him for the border plan last year, saying that anyone who wants to build walls rather than bridges is "not Christian".
The remark incensed the then Republican candidate, who said it was "disgraceful" that the pontiff should question his religious faith.
The embodiment of bullish, free-wheeling capitalism, Donald Trump made his fortune from investing in property and other ventures around the world and wants to slash taxes for the rich.
Pope Francis, in contrast, has repeatedly warned that the excesses of the global capitalist system are leaving millions of people behind, fueling social tensions and harming the planet.
Pope will keen an 'open mind'
Pope Francis said earlier this month that he would keep an open mind and not pass judgement on the President until first listening to his views.
"Even if one thinks differently we have to be very sincere about what each one thinks," he told reporters while flying back to Rome after a visit to Portugal.
"I will say what I think and he will say what he thinks. There are always doors that are not closed. We need to find the doors that are at least partly open, go in, and talk about things we have in common and go forward, step by step," he said.
Senior Vatican figures have said the Pope will try to change President Trump's opinion about climate change.
Monsignor Marcelo Sanchez Sorondo, the head of the Pontifical Academy of Sciences, said: "This President has already changed his mind on several things, so perhaps he will on this as well.
"The President claims to be a Christian, and so he will listen to him," said Monsignor Sorondo, who is seen as being close to the Pope. Mr Trump was raised as a Presbyterian but attends church rarely.
The timing of the meeting on Wednesday is significant. President Trump's audience will be at the unusually early hour of 8.30am.
The White House dithered for weeks about whether to request a papal audience prior to the President heading to the G7 summit at Taormina in Sicily.
When the request was finally made, the Vatican had to squeeze the appointment into the Pope's busy schedule, so that he will have plenty of time to prepare for his weekly general audience in St Peter's Square.
After his meeting with the Pope, President Trump and his wife Melania are expected to be shown the Sistine Chapel.
The First Lady will then visit the Bambin Gesu (Baby Jesus) Hospital in Rome to meet sick children.
Ivanka Trump will go to the Sant' Egidio Community, a Catholic charity, to discuss human trafficking and meet women who were forced into prostitution.
The President will meet Sergio Mattarella, Italy's president, and Paolo Gentiloni, the prime minister, before boarding a plane to Brussels for a Nato meeting.