Anna was the daughter of Manuel Angelos Philanthropenos, Caesar and governor of Thessaly.^[1] Manuel ruled Thessaly from c. 1390 until it was conquered by Bayezid I of the Ottoman Empire in 1394.

Her paternal grandfather, or more likely uncle, was Alexios Angelos Philanthropenos, also a Caesar, who was governor of Thessaly from c. 1373 to 1390. Her maternal grandmother, or more likely aunt-in-law, was Maria Radoslava.^{[citation needed]}

Gulkhan-Eudokia of Georgia, Manuel's first wife and Empress consort of Trebizond died 2 May 1395.^[2] On 4 September of that year, Eudokia, Manuel's sister and the widow of Tadjeddin Pasha of Sinop and Emir of Limnia, arrived from Constantinople at Kordyle with Anna Philanthropene and Theodora Kantakouzene; these women had come to wed, respectively Manuel III and her nephew Alexios. The combined wedding took place the following day in Trebizond.^[3]

The ambassador to Tamerlane, Ruy Gonzáles de Clavijo met Manuel III and his family April 1404 while passing through Trebizond, and alludes to Anna Philanthropene as being alive.^[1] Manuel died on 5 March 1417; whether Anna survived him is unknown. Thierry Ganchou claims to have identified a son of Manuel and Anna, who was alive as late as 1423, and old enough to marry Eudokia, the daughter of the protostrator Manuel Palaiologos Kantakouzenos.^[4]