During that time, Kercher's American roommate Amanda Knox and Knox's boyfriend at the time, Italian citizen Raffaele Sollecito, were twice convicted and twice acquitted of murder for their alleged role in ending Kercher's life.
On Monday, Italy's highest court issued the last word on the case in the form of a 52-page reasoning to justify why it decided to definitively throw out the convictions last March.
Citing "glaring errors," "investigative amnesia," and "guilty omissions," the five-judge panel said that the prosecutors who won the original murder conviction failed to prove a "whole truth" to back up the scenario that Knox, Sollecito and Ivory Coast native Rudy Guede killed Kercher.
That original murder conviction in 2009 was overturned on appeal in 2011, but the high court threw out the acquittal two years later and ordered a new appellate trial, which found the pair guilty once again in 2014.
That second guilty verdict was thrown out in March by Italy's high court, finally ending the legal back-and-forth.
No way to find the truth
In explaining the somewhat unconventional choice to throw out the case without ordering a new trial -- which is how high courts in Italy generally rule when not confirming guilt -- the judges said that due to the reasonable doubt and shoddy police work when initial evidence was collected, there was simply no way to go back and find any real truth.
The judges found there was too much potential for contamination of the key forensic evidence.
That included a knife with DNA on it originally attributed to both Knox and Kercher, and Kercher's metal bra clasp, which some experts said had traces of Sollecito's DNA on it.
The knife, the judges said, was kept in a simple cardboard box by forensic police and the bra clasp sat for nearly six weeks on the floor in the room where Kercher was found before it was collected.
The judges also agreed that while Knox testified that she was in the house at the time of the murder, the prosecution never effectively proved she was in the room where Kercher was killed, citing an "absolute lack of evidence related to their biological traces in the room or on the body of the murder victim."
In the end, the high court determined that reasonable doubt prevailed.
A hasty investigation
The various murder trials and appeals came to different conclusions as the result of "stunning weakness or investigative amnesia and of guilty omissions of investigative activity," the court found.
Had it not been for these mistakes, the court determined, "in all probability, the defendants' guilt, if it was to be, could have been determined from the earliest stages."
Instead, the court blamed the media and high profile attention on the case for putting pressure on local authorities in Perugia, effectively causing what the judges called a "sudden acceleration" during the initial stages of the investigation.
"Certainly the unusual hype of the story, due not only to the dramatic mode of death of a 22-year-old, so absurd and incomprehensible in its genesis, but also to the nationality of the people involved meant international repercussions," the judges wrote. "That has meant that the investigations suffered a sudden acceleration, which, in the frantic search for one or more culprits to be delivered to international public opinion, certainly did not (facilitate) seeking the truth."
Meanwhile, Guede, who was convicted in a fast-track trial in 2008, is nearly halfway through his 16-year sentence.
He remains the lone person convicted of a murder that his own panel of high court judges ruled was committed by three people.
As a matter of law, that means there are two killers still at large, which is a point Guede's lawyers have been arguing since the case was closed in March.
The high court did end its lengthy ruling by upholding a slander conviction against Knox, stemming from her initial accusation that Patrick Lumumba, her Congolese pub boss, was involved in Kercher's murder.
The slander charge carries a three-year sentence, which Knox served during her four-year incarceration. That greatly limits potential damages she can claim against the Italian state for wrongful incarceration.
Sollecito, however, is already preparing a libel suit for his four years in precautionary custody, which his lawyers argue was unjust and for which the state should compensate him.
On Monday, Knox issued a statement on her website saying that she is "deeply grateful that the Italian Supreme Court has filed its opinion and forcefully declared" her innocence.
"This has been a long struggle for me, my family, my friends, and my supporters. While I am glad it is now over, I will remain forever grateful to the many individuals who gave their time and talents to help me," her statement said.
Kercher's family, which has long held that Knox and Sollecito were involved in Meredith's murder, said through their lawyer that they, too, can now hope to move on.