Faith Marley, from the Leith area of Edinburgh, was last seen on CCTV meeting a man in Glasgow.
Police said the teenager travelled from the Scottish capital on a Citylink number 900 bus which arrived at Buchanan Bus Station in Glasgow shortly after 11.05am on Wednesday.
She was then spotted on CCTV meeting a man shortly after 11.20am before the pair left the bus station in the direction of North Hannover Street.
Police said they remain “very concerned” for Faith, and are hoping to identify the man she was with to help them in their search.
Faith has been described as about 5ft 7ins, of medium build and has dark blonde shoulder-length hair.
She was wearing a black hooded top, leggings and black and white high-top converse shoes at the time she was last spotted.
The man she was seen with has been described as white, has dark hair and is likely between the age of 20 to 30 years old, police said.
He was wearing a grey jumper, black trousers and black shoes and was seen pulling a white or silver case or box with a blue bag on top of the handle and carrying a dark-coloured backpack.
Chief Inspector Cath Thorburn said: “This sighting in Glasgow is now the most recent confirmed sighting of Faith.
“While nothing from our enquiries suggest she has come to any harm, she has not now been seen since Wednesday morning and we remain very concerned for her.
“We would urge anyone who believes they may have seen or heard from Faith at any time since Wednesday to get in touch urgently.
“We are working to identify the man seen in her company leaving Buchanan Bus Station as he may have information which could help. If you know who he is or if you recognise yourself please come forward.
“If you can help, please call us immediately on 101, quoting reference number 0385 of Wednesday, 15 March, 2023.”