His father was a physician who descended from a branch of the noble Eastern Roman family of Melissenos that had left Crete in the 15th century and settled on Cephalonia.

[3] He received a thorough education in his youth and was fluent in many languages, including Russian, German, Italian, French, and Turkish, as well as his native Greek; he also knew some Latin and English.

His efficient command helped Russian forces prevail against a fourfold numerical superiority of the Ottomans at Khotin, Larga, and Kagula.

After the ascension of Emperor Paul, Melissino was put in charge of the entire Russian artillery but died the following year.

He was a prominent figure in Saint Petersburg society; he spoke several languages, fenced and danced well, and was an authority on the theater.