Manfredi was born in Castro dei Volsci, Frosinone into a humble family of farmers. His father recruited in Public Safety, where he reached the rank of Maresciallo, and in the early 1930s, he was transferred to Rome, where Nino and his younger brother Dante spent their childhood in the popular neighborhood of San Giovanni. In 1937, he became seriously ill with bilateral pleurisy, and after a doctor gave him only three months to live, he remained several years hospitalized in a sanatorium; there he learned to play a banjo built by himself and he entered the musical band of the hospital. To please his family in October 1941, he enrolled at the university in the Faculty of Law, but already in the same year he showed an interest and a natural inclination for the stage, making his debut as a presenter and an actor in the theater of a parish in Rome.
After 8 September 1943, in order to avoid conscription, he took refuge for a year with his brother in the mountains above Cassino; returned to Rome in 1944, he resumed his university studies and, at the same time, he enrolled at the National Academy of Dramatic Art. In October 1945, he graduated in law with a thesis in criminal law, without ever practicing the profession, and in June 1947, he graduated from the academy.
