Fratoianni was born in Pisa to parents from Ururi, province of Campobasso, Molise, Southern Italy.

[2] Fratoianni is considered the leader of the left-wing faction, which opposed an alliance with the centre-left Democratic Party when it was led by Matteo Renzi.

Fratoianni's aim is to create a left-wing party inspired by the Greek Syriza of Alexis Tsipras and the Spanish Podemos of Pablo Iglesias Turrión.

[3][4] He lives in Foligno, in province of Perugia, with his wife Elisabetta Piccolotti (former national spokesperson for the Young Communists and since 2022 deputy of the Italian Left)[5][6][7], with whom he has a son, Adriano, born in 2013.

Nicola and Elisabetta got married civilly in Foligno on 3 September 2019, in front of Nichi Vendola (his friend and close political collaborator), who celebrated the wedding.