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.
Her disappearance is being treated as suspicious.
A targeted search will begin on Friday in and around Mount Clear, based on an area highlighted by 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 currently in the process of reviewing about 12,000 hours of CCTV footage and following up over 500 separate pieces of information.
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.
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.
"Given the extensive and detailed search that has already been undertaken, and the fact no sign of Samantha or her personal belongings has been located, we have ruled out any type of medical incident," he said on Friday.
"There is also nothing to indicate that Samantha left the area of her own accord."
He 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.
"Finally, it's important that people continue to avoid unnecessary and unhelpful speculation because we don't want that to detract from the genuine investigation or potentially prevent anyone coming forward with information because they have a misconception about what has happened to Samantha.
"Police remain open to any and all possibilities, so if you know something or have seen something, then we want to hear from you."
Ms Murphy is described as mentally and physically fit and was training for an upcoming race by doing 15km runs.
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