[3] Among his siblings were the Despotess of Serbia Irene Kantakouzene, the Empress of Trebizond Helena, and the unnamed wife of King George VIII of Georgia.
He assisted in the construction and defense of the Castle of Smederevo that his sister and brother-in-law Đurađ Branković began in 1430; for a while he commanded the garrison at that fortification.
The historian Donald Nicol, who studied the Kantakouzenos family, believes that George was not present at the first Turkish capture of the fortress by Murad II in 1439, when defense of Smederevo was in the hands of his brother Thomas, nor at its final siege and capture by Mehmet II on 20 June 1459.
Spandounes claimed him as his maternal grandfather, and elsewhere describes him as the grandson of the Emperor John VI Kantakouzenos.
Nicol believes Spandounes is in error, and the Emperor John VI was his great-grandfather and Matthew Kantakouzenos his grandfather.