Rubio will face fellow senators at his confirmation hearing in what is likely to be among the least contentious sessions for Trump's motley array of nominees.
In excerpts from his opening remarks, Rubio will lay aim at China -- which outgoing President Joe Biden has also called a competitor but nevertheless sought to engage.
The longtime hawk will firmly reject a key tenet of Biden's -- prioritizing a ruled-based, US-led "liberal world order" -- in favor of Trump's belief in "America First."
"The postwar global order is not just obsolete; it is now a weapon being used against us," Rubio will say, according to the prepared remarks.
"We welcomed the Chinese Communist Party into this global order. And they took advantage of all its benefits. But they ignored all its obligations and responsibilities," Rubio was to say.
"Instead, they have lied, cheated, hacked and stolen their way to global superpower status, at our expense."
While highlighting China, Rubio's remarks also say that in "Moscow, Tehran and Pyongyang, dictators sow chaos and instability."
Rubio will call for a foreign policy driven solely by whether decisions make the United States safer, stronger and more prosperous.
"While America far too often continued to prioritize the 'global order' above our core national interests, other nations continued to act the way countries always have and always will, in what they perceive to be in their best interest."
Rubio, the son of working-class Cuban immigrants, would become the first Hispanic and first fluent Spanish speaker to be the top US diplomat.
- Expected to coast to confirmation -
Other nominees facing Senate hearings Wednesday include Pam Bondi, tapped for the top law enforcement job of attorney general, who served the same role in Florida and personally defended Trump in his first impeachment trial.
Trump named her after his first choice, Matt Gaetz, withdrew following allegations that he paid for sex, including with an underage girl, at drug-fueled parties.
Little controversy surrounds Rubio, a three-term senator generally well-liked by his colleagues and known for his ease in public appearances.
He clashed bitterly with Trump when he challenged him for the 2016 nomination -- with the future president mocking him as "Little Marco" -- but he has come back into good graces.
He is expected to get to work quickly, with sources saying preparations are underway for an immediate four-way meeting on Tuesday in Washington with Rubio's counterparts from the Quad -- Australia, India and Japan.
The Quad has long been seen by China as a US-led platform for the four democracies to encircle it, despite Quad leaders' denials.
Rubio's appearance comes a day after the Biden administration announced it was removing Cuba from a list of state sponsors of terrorism as part of a deal that will free imprisoned protesters.
The move comes almost exactly four years after Trump, on leaving office, put Cuba back on the blacklist.
Rubio, whose parents fled Cuba before Fidel Castro's 1959 revolution and strongly opposed the communists, for years has pushed for tough action against Cuba and other leftist-run Latin American nations such as Venezuela.
Another nominee set for a senate hearing on Wednesday is Kristi Noem as homeland security secretary.
As the governor of South Dakota, Noem raised her profile among Trump supporters with her opposition to Covid pandemic restrictions, but later raised controversy by revealing in a memoir how she killed her family's dog.
Pentagon nominee Pete Hegseth faced a grueling hearing Tuesday, including questioning over his views on women in combat and allegations of sexual abuse, which he denies.
Some of the most potentially fiery hearings are yet to be scheduled, including for vaccine conspiracy theorist Robert F. Kennedy Jr. as health and human services director and Trump stalwart ally Kash Patel to head the FBI.
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