Manuel was either the son or the brother of the Caesar Alexios Angelos Philanthropenos, who had ruled Thessaly since the early 1370s, succeeding him upon his death c. 1389/1390.
Like Alexios, he recognized the suzerainty of the Byzantine emperor, and was given the title of Caesar in return.
[1][2] In 1389, he (or Alexios, if he was still living) sent aid to the ruler of Ioannina, Esau de' Buondelmonti against the Albanian tribes of Epirus, and their joint forces scored a major victory over them.
[4] Either he or (less likely) Alexios was the grandfather of the Serbian ruler Mihailo Anđelović and the Ottoman Grand Vizier Mahmud Pasha Angelović.
[5] His daughter Anna Philanthropene married Emperor Manuel III of Trebizond.