Amanda Knox and Raffaele Sollecito spent four years in jail in Italy for murder but were freed on appeal in October 2011, largely on the grounds DNA evidence was flawed.
Prosecutors appealed and the Court of Cassation overturned the acquittals.
Ivory Coast national Rudy Guede was convicted in a separate trial and sentenced to 16 years.
He was found guilty of sexually assaulting and stabbing Meredith Kercher. Rudy Guede admitted being at the house on the night of the killing in November 2007, but denies murder.
Meredith Kercher, from Coulsdon, south London, had been on a year abroad from Leeds University when she was found semi-naked in her bedroom and with her throat cut in the cottage she shared with Amanda Knox.
Prosecutors believed Meredith Kercher was killed in a brutal sex game that went wrong.
Addressing the court on Monday, they urged the judges to “make sure the final curtain does not drop on this shocking and dire crime”.
Amanda Knox’s Italian lawyer, Luciano Ghirga, said on Monday her client was “very anxious” about the latest hearing.
Amanda Knox lives in Seattle and a retrial is likely to take place in absentia, as the US is unlikely to extradite her, analysts say.
Amanda Knox and Raffaele Sollecito were originally sentenced to 26 and 25 years in prison for killing and sexually assaulting Meredith Kercher.
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