Knox may be ordered to return to Italy for the retrial.
If she refuses, the Italian government could appeal to the U.S. government for her extradition.
But even if it does, Knox might still not end up before an Italian court.
U.S. officials might reject such a request because it violates the U.S. legal principle that a criminal defendant can't be tried twice on the same allegation, said Joey Jackson, a contributor for HLN's "In Session."
Italy lacks the absolute prohibition present in U.S. law preventing authorities from retrying a criminal defendant who has been acquitted of a charge.
"We have principles that are well-founded within our Constitution, one of which is double jeopardy," Jackson said. "So as a result of that, I think it would be highly objectionable for the United States to surrender someone to another country for which justice has already been administered and meted out. So I don't think or anticipate that that would happen."
Another lawyer for Knox, Luciano Ghirga, said Monday that her client was confident in the Italian legal system and hoped one day to return to Italy as a free woman.
The Supreme Court did not order her retrial Tuesday on a charge of defamation.
Knox's conviction for defaming Patrick Lumumba, a club owner whom she accused of killing Kercher, was upheld in October 2011 by the same appeals court that cleared her of murder.
The case began in 2007, after Knox moved to Perugia to study at the University for Foreigners of Perugia for one year.
Knox, then 20, shared a room with British student Kercher.
That November, Kercher's semi-naked body was found at the home, with her throat slashed.
Police arrested Knox and Sollecito, who was her boyfriend at the time.
Two years later, they were convicted of murder, but they were cleared when they appealed the verdicts in 2011.
'Lack of evidence'
In legal paperwork published in December 2011, the judge in the case wrote that the jury had cleared the pair of murder for lack of evidence proving they were guilty.
Knox's family said last year the appeal was unwelcome, but no cause for concern.
"The appeal of Amanda's acquittal by the prosecution was not unexpected as they had indicated from the day of the verdict that they would appeal," a family statement in February 2012 said.
Knox has spent the last year and a half trying to resume a normal life, studying creative writing at the University of Washington in Seattle, her hometown, according to family spokesman Marriott.
She also has written a book on her ordeal, titled "Waiting to be Heard," which will be published next month.
According to Harper Collins, Knox "tells the full story of her harrowing ordeal in Italy -- a labyrinthine nightmare of crime and punishment, innocence and vindication -- and of the unwavering support of family and friends who tirelessly worked to help her win her freedom."
The publisher did not have any immediate response to the news that Knox now faces a retrial.
Francesco Sollecito, Raffaele's father, told CNN in a phone interview last year that the family was "not happy about the decision (to appeal). My son is trying to get back to normal life."
"We can do very little in this situation," he said, but as Italian citizens, they would have to accept the court's decision.