Vicky Glass was last seen being dropped off by a taxi driver at 4am on September 24 2000 in Middlesbrough.
Her body was discovered in a stream in the village of Danby, North Yorkshire, six weeks later.
Since then four people have been arrested on suspicion of murder and all have been released with no further action taken.
Cleveland Police has reviewed the case and a new team from the Historical Investigation Unit led by Detective Chief Inspector Peter Carr is reinvestigating.
They will use new forensic techniques, speak to potential witnesses and look at over 2,000 hours of CCTV footage from the time of her disappearance.
Ms Glass, who was 21 when she was murdered, was much-loved by her family and had a happy childhood.
Detectives said her life changed when she was 18 and she was exploited by others who led her into drugs and pressured her into sex work.
It was while she was doing this on the streets of Middlesbrough that she was murdered and police are still keen to find out who she had been with that night.
Detectives have launched a website, www.vickyglass.co.uk, containing information about her and the inquiry, in a bid to appeal for information and to put the case back in the spotlight.
Mr Carr said: “Much work has been carried out over the last 12 months on Vicky’s case, including a detailed review of the original investigation.
“This review identified over 300 recommendations, with the main one being that a reinvestigation should be undertaken.
“We believe that there are a number of lines of inquiry which can be pursued and by using modern investigative and forensic techniques, we hope to get justice for Vicky and her family.
“We have new and significant lines of inquiry and will be speaking to people connected to the case and trawling through CCTV from the time period to help us with any new leads.
“Vicky was a vulnerable woman who was exploited by men, she was not a sex worker by choice, but forced by circumstance as a young adult.
“She had her whole life ahead of her, was loved by her family, she did not deserve to die and we will continue to seek justice for her murder.”
In a statement her family said: “We feel the loss of Vicky every day, she deserves justice and hope that this reinvestigation puts those responsible behind bars.
“She did not deserve to have her life taken, no-one had the right to do that.”
Anyone with information can call the investigation team directly on 01642 301773, Cleveland Police on 101 or Crimestoppers anonymously on 0800 555 111.