The Court of Cassation's decision to overturn the acquittals of Knox and Sollecito sends the matter to an appeals court in Florence, the ANSA news agency reported.
In a statement, Knox, 25, said it was "painful" to hear the decision "when the prosecution's theory of my involvement in Meredith's murder has been repeatedly revealed to be completely unfounded and unfair."
"I believe that any questions as to my innocence must be examined by an objective investigation and a capable prosecution," she said. "The prosecution responsible for the many discrepancies in their work must be made to answer for them, for Raffaele's sake, my sake, and most especially for the sake of Meredith's family."
"Our hearts go out to them," Knox said in the statement. "No matter what happens, my family and I will face this continuing legal battle as we always have, confident in the truth and with our heads held high in the face of wrongful accusations and unreasonable adversity."
Francesco Maresca, the Italian lawyer representing Kercher's family, pumped his fist in satisfaction when the Court of Cassation announced it had put aside the acquittals of Knox and Sollecito, ANSA said.
Knox and her then-boyfriend Sollecito were convicted of the 2007 killing of Kercher, a student from Britain, while the two women were exchange students rooming together in Perugia. However, the conviction was thrown out by an appeals court in 2011. Prosecutors said Knox, Sollecito and a third person, Rudy Guede of the Ivory Coast, killed Kercher in a sex game gone wrong.
Knox, living in Seattle, isn't required to return to Italy for the trial, ANSA said. If she is convicted again, that ruling would be appealed to the Supreme Court.
In final arguments before Italy's Supreme Court Monday, Knox's lawyer Carlo Dalla Vedova told the court, "This trial started with an error and the prosecution continues to insist in the errors even in an attempt to convince the Supreme Court that the recourse should be accepted."
Knox and Sollecito were sentenced to 25 years in prison. Knox also received an extra year on a slander conviction for falsely accusing her former boss, Patrick Lumumba, as Kercher's killer. During Monday's proceedings, Knox's lawyers also asked that her slander conviction be overturned.
Prosecutors and a lawyer for Kercher's family said the appeals court judges "lost their way" in reviewing the evidence and that Knox and Sollecito should be retried for Kercher's killing.
Guede was convicted in Kercher's death and is serving a 16-year prison term.
After her release from prison in 2011, Knox returned to her hometown of Seattle and is a student at the University of Washington. Her memoir, "Waiting to be Heard," is expected to be published April 30.
Sollecito has been living in Verona, where he is working toward a degree in computer engineering.