Grave fears are held for the welfare of Angie Fuller who was last seen in Alice Springs on January 9 driving a red Toyota Corolla.
The car was found abandoned the following day on The Tanami Road, northwest of the town.
Police used drones, a helicopter, all-terrain vehicles and foot patrols to scour about 400 square kilometres for two weeks but found no trace of the 30-year-old mother of two.
"We are now shifting from a missing persons search to a suspicious investigation," Assistant Commissioner Michael White told reporters on Tuesday.
"We believe at this stage that Angie is missing because of third party intervention ... as a result we are investigating and treating it as a homicide."
Asst Comm White suspended the search and rescue component earlier in the day.
"We've certainly spoken to a lot of people and there are some parties that are persons of interest, who were involved prior to the last sighting of Angie," he said.
Ms Fuller was last seen about 6.40pm at a truck stop north of Alice Springs.
Police also believe Ms Fuller was involved in a vehicle incident on The Tanami Road about 15km west of the Stuart Highway in the early hours of Tuesday morning on the the 10th.
"Two vehicles involved (and) there was some sort of dispute and as a result one of the cars was run off the road," Asst Comm White said.
"We've spoken to all the parties (and) that's the point when we believe Angie became separated from everyone else."
Police said previously that Ms Fuller had not accessed her bank accounts since going missing and had not engaged with social media of any kind.
They also spoke with a man who claimed to be her boyfriend in a rambling video posted on social media in the days after she went missing.
In the video, the man said the pair were run off the road and then shot at by a gang before fleeing into the bush.
Asst Comm White said the man was a person of interest and the pair were together when she was last seen.
The search area was unusually green because of heavier rain over recent months and while that had thrown up additional challenges it gave police hope that Ms Fuller could have water available.
