The 51-year-old mother of three left her home at Eureka Street in Ballarat East on February 4 to go jogging and has not been seen since.
Detective Acting Superintendent Mark Hatt said police were keeping an open mind over Ms Murphy's disappearance, but said the most likely scenario was that it involved one or more parties.
He said police had ruled out any type of medical episode and there was nothing to indicate she had left the area on her own accord.
"Unfortunately given the time and the fact we've found no trace of her, we do have severe concerns and are very doubtful that she is still alive," Det Supt Hatt told reporters in Mount Clear on Friday.
"We are looking into absolutely everything ... this is the utmost priority for Victoria Police and we are throwing a lot of resources at it."
He wouldn't be drawn on the number of suspects in the case, but did say that Ms Murphy's husband is not a suspect "at this stage".
The detective also wouldn't comment on whether police had uncovered links to outlaw motorcycle gangs or the financial standing of the car repairs business owned by the Murphys.
A targeted search by between 20 and 40 personnel will begin on Friday in a "fairly small area" in Mount Clear, based on intelligence derived from phone data.
Extensive searches have been conducted throughout the Canadian Forest area since Ms Murphy's disappearance almost three weeks ago, however no trace of her has been located.
Experienced detectives from a number of units across the force's crime and counter terrorism command were deployed to join the missing persons squad, which is leading the investigation.
Investigators are reviewing about 12,000 hours of CCTV footage and following up over 500 separate pieces of information.
Det Supt Hatt moved to reassure Ballarat locals and Victorians on a broader scale that detectives were doing all they could to provide some answers to Ms Murphy's family.
"I encourage anyone who does have information that could be relevant to this investigation – whether that's a person or vehicle seen in the area on that day, something unusual such as a damaged vehicle or property – to please come forward and speak to police or provide the information via Crime Stoppers," he said.
Police are continuing to ask everyone in the Ballarat East and Mount Helen areas, particularly around the Canadian Forest, to check their CCTV for any possible sightings over the past three weeks.
Detectives are also urging anyone travelling through the area, particularly between 7am and 7pm on Sunday, February 4, who may have dash-cam footage to also check this for possible sightings.
Ms Murphy is described as mentally and physically fit and was training for an upcoming race by doing 15km runs.
A community search effort is expected to take place on Saturday, without police involvement.
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