12-year-old Estefany Montino and 13-year-old George Villareal have been missing since Monday night.
Their parents believe the two children, who attend McAuliffe Middle School, are together.
"I can't imagine that they're in very good shape right now, said Jamie Tibbetts, the teen’s father.
The two children were last seen around 8pm Monday night in the 5500 block of Ghost Hawk on the city's Southwest side.
Montino's mom says she went to drop off a movie at a Redbox, and when she went back minutes later, her daughter was gone.
She went on to say her daughter left the family home with George.
The Montino and Villareal families are working with the Heidi Search Center and San Antonio Police Department's Missing Persons Unit to help find their children.
If you have seen the children, call the Heidi Search Center at (210) 650-0428 or the SAPD Missing Persons Unit at (210) 207-7660.
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