Rubio, the son of Cuban immigrants who would be the first US secretary of state fluent in Spanish, from his earliest days has been a vociferous opponent of the communist government in Havana and other Latin American leftists, including in Venezuela.
In recent years the senator from Florida, whose nomination has been reported by multiple US media outlets but not yet confirmed, has become one of the most outspoken senators against Beijing.
His efforts have included championing Taiwan, moving to restrict Chinese business operations in the United States and leading legislative measures to punish the Asian power over its treatment of Hong Kong and the Uyghur minority.
Rubio has also long joined Republicans in their fervent support for Israel and hard line on Iran's clerical state.
Yet for all of his adamant views on the world, the baby-faced 53-year-old was once seen as a rising star in a more moderate Republican Party that would reach out to minorities and suburban swing voters.
After Barack Obama won reelection in 2012, Rubio, then an ambitious first-term senator, sought to work across party lines to overhaul the immigration system and offer a more humane, legal pathway to undocumented immigrants.
Trump has won his second term on a starkly different platform -- mass deportation -- and Trump crushed Rubio's own presidential ambitions in 2016 in the Republican primary.
Rubio, seeking to fight Trump at his level, told a Virginia rally during that campaign: "Have you seen his hands?"
"You know what they say about men with small hands," Rubio said tauntingly.
The crowd erupted. But Rubio's low blow antagonized Trump, who would mock him as "Little Marco."
"He referred to my hands -- if they're small, something else must be small," Trump said days later at a Republican debate, as Rubio stood just feet away. "I guarantee you there's no problem."
- Future 'defined' by Asia -
Rubio, much like Vice President-elect JD Vance, has looked at the Republican electorate and become a full-throated supporter of Trump, much to the president-elect's delight.
In an interview on Catholic-oriented EWTN after Trump's victory over Vice President Kamala Harris, Rubio backed Trump's assertion that the United States is overextended and should focus on rivalry with China.
Speaking like Trump, if more diplomatically, Rubio said Ukraine had fought valiantly but hit a "stalemate" against Russian invaders and that the United States should show "pragmatism" rather than sending billions of dollars more in weapons.
"I don't like what Vladimir Putin did, and we do have an interest in what happens there," Rubio said of Russia's president.
"But I think the future of the 21st century is going to largely be defined by what happens in the Indo-Pacific."
Rubio in the Senate has led efforts to arm Taiwan, the self-governing democracy claimed by Beijing. He has called for direct shipments of US munitions and advanced military technologies in hopes of deterring China, rather than simply selling weapons to Taiwan.
In July, Rubio insisted that a second Trump administration would support Taiwan after Trump in an interview appeared to say that the island needed to pay the United States "protection" money.
- 'Exceptional' America -
Rubio advanced quickly in politics, winning a city election in 1998 five years out of college and becoming speaker of the Florida House of Representatives at age 34.
A Roman Catholic, he has four daughters with his childhood sweetheart, Jeanette Dousdebes, a former cheerleader for the NFL's Miami Dolphins.
Rubio has frequently spoken of his working-class background -- a father who worked as a bartender, coming home late, and a mother who was a cashier.
In a 2012 interview with Time, Rubio recalled how his mother left him a voice message urging him not to "mess" with undocumented immigrants, pleading that they are "human beings just like us."
Now that he is poised to be America's top diplomat under the anti-immigration Trump, Rubio is likely to take another part of his family's message -- their steadfast opposition to communism.
In a 2012 memoir, "An American Son," Rubio recounted how his cigar-smoking grandfather told him how the United States was a beacon to the world's oppressed.
"My grandfather didn't know America was exceptional because he read about it in a book. He lived it and saw it with his own eyes."
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