Maria was the daughter of the Serbian Emperor of Thessaly, Simeon Uroš, the half-brother of Emperor Stephen Uroš IV Dušan of Serbia (Nemanjić dynasty), and Thomais Orsini. Her maternal grandfather was John Orsini of Epirus.
Maria was a descendant of the Serbian Emperor of Thessaly, Simeon Uroš, and her uncle was King Stephen Dušan IV of Serbia from the Nemanjić dynasty, while her mother's family ties were to Thomais Orsini. Her maternal grandfather was John Orsini of Epirus.