Shyanne-Lee Tatnell was last seen on the night of April 30 when she was captured on CCTV near the Henry Street Bridge in Launceston.
Tasmania Police on Wednesday launched a fresh search operation at two locations, including 50 sq km of bushland near Nabowla, about 50km northeast of Launceston.
About 160 personnel have been deployed, including 20 search and rescue personnel, SES volunteers, helicopters, people on horseback, all-terrain vehicles, drones and police recruits.
The search, understood to be the largest of its kind in Tasmania's north, is expected to last several days.
A specialist cadaver dog from NSW is scouring the North Esk River.
Tasmania Police detective acting inspector Andrew Hanson said a "specific line of inquiry" was being followed.
He said police had identified all cars of interest in the Henry Street area at the time Shyanne-Lee went missing and drivers had been spoken to.
"Our investigative team has spent considerable time scouring CCTV, interviewing witnesses and meticulously following up every lead," he said on Wednesday.
"Our search efforts this week are as a result of our commitment to locate Shyanne-Lee. We are doing everything in our power to make that happen."
Investigators in early June forensically tested a car relating to a person of interest, but no link to Shyanne-Lee was found.
She was last seen wearing bike shorts and a cream hoodie with dark writing across the chest and shoulder.
Shyanne-Lee is described as about 160cm tall with a slim build and blonde hair.
She had been staying in youth accommodation for the two weeks before her disappearance and was on her way to visit a friend in nearby Ravenswood.
Anyone with information has been urged to contact police.
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