Theodora's parentage is described by the Byzantinist Donald Nicol as "obscure".
However, Thierry Ganchou has provided evidence that indicates Theodora was the oldest daughter of Theodore Palaiologos Kantakouzenos, uncle of emperor Manuel II Palaiologos, and Euphrosyne Palaiologina, and names her brothers in order of birth as Demetrios, protostrator Manuel, George, megas domestikos Andronikos, and Thomas.