In the days leading up to her disappearance, Layla Santanello had been staying with friends after a falling out with her boyfriend Michael Thompson at their shared home at 562 Dale Street in Kingsport. The relationship had become strained after Thompson discovered Layla had started seeing someone else. On June 25, 2023, Layla checked into the Americourt Hotel at 1900 American Way in Kingsport.

On June 26, guests at the Americourt reported seeing Layla going door to door in an apparent state of distress. She declined offers of help from multiple strangers. That morning she had an altercation with an unknown person and told a friend, "I have to take care of something." Motel staff threatened to evict her because of the commotion. Around midday on June 26, Layla walked off toward nearby woods. Warehouse workers in the area reported seeing her from a distance. Her family believes she was frightened and running from someone she had encountered at the hotel.

The last confirmed sighting of Layla Santanello occurred at approximately 6:15 a.m. on June 27, 2023, in a field adjacent to the Americourt Hotel. She was barefoot, wearing a white tank top and black leggings. She was last seen walking in the direction of the Kingsport Greenbelt, a trail system that runs through the city. She was not seen again after that point.

A family member reported Layla missing to the Kingsport Police Department on June 27 after they were unable to reach her. Investigators were subsequently able to trace her movements from the Americourt to the Greenbelt but found no further confirmed sightings beyond the 6:15 a.m. field sighting. An early lead suggesting she had been seen at the Marble Slab Creamery at East Stone Commons was later ruled out by KPD; the woman seen there was identified as someone else.

In the weeks following her disappearance, Layla's family began receiving fraudulent Cash App requests from someone using Layla's account, beginning July 10 and continuing through August 12. One message contained the character string "twlmg," which the family interpreted as "they won't let me go." Another read: "We have Layla. She owes a drug debt, and if she doesn't pay, you'll find her chopped up into pieces." The IP address and device associated with the Cash App account were traced to the home of Michael Thompson. Thompson was arrested in March 2024 and charged by the Sullivan County Grand Jury with Extortion and Identity Theft. KPD has confirmed that no evidence connects Thompson to Layla's disappearance itself.

As of April 2026, Layla Santanello has been missing for nearly three years. Kingsport Police reportedly told Layla's stepmother Brittany Zeitler in December 2023 that they believe they know what happened, who is responsible, and roughly where Layla is, but could not yet share details. No charges have been filed in connection with her disappearance. The case remains active and classified as endangered missing.