The 17-year-old was stabbed to death after a night out in Bath in June 1984. More than 90 people were arrested but no-one was charged with her murder.
Avon and Somerset Police say forensic advances could lead to new clues in the case.
Det Insp Julie Mackay said they were contacting hundreds of people to ask them for DNA samples.
The A-Level student was last seen alive in the early hours of Saturday June 9 in Broad Street after deciding to walk home alone.
Her body was discovered later that morning by a milkman, close to a block of garages in St Stephens Court, Lansdown.
Since then, new forensic techniques have enabled police to develop of a full DNA profile of the suspected killer.
"We are now cross-checking that DNA with that of all people with links with Melanie or who we know were in Bath at the time and may be of interest," said Det Insp Mackay.
"It is a long and laborious process but I believe Melanie's murderer is within that group."
Police have also appealed for a "significant witness," who contacted police five years ago, to come forward again.
Det Insp Mackay said the person had "important information".
"All we need is a name," she said.
Police claim they are close to finding the killer of teenager Melanie Road, 30 years after her death.