In his youth he fought in the service of both the House of Savoy and the Spanish viceroyalty, but he eventually withdrew from military life to lead a patrician's existence in his villa overlooking the Gulf of Naples.

He founded the Accademia degli Oziosi in Naples in 1611, and he actively promoted the establishment of the Collegio de' Nobili for the education — under the direction of the Jesuits — of young Neapolitan aristocrats.

[2] This coltissimo cavaliere — as the eighteenth-century literary historian Girolamo Tiraboschi called him — knew a great many of the leading Italian letterati of the age.

He numbered among his acquaintances Paolo Beni (the influential literary critic and theorist), Giambattista Della Porta, Antonio Bruni, Tommaso Campanella, Torquato Accetto, Galileo Galilei, and many other writers, artists, and philosophers up and down the peninsula; and his circle in Naples itself included practically all major figures of the city's literary life.

By late 1638, when John Milton visited Manso in Naples, his aging host had become “a living symbol of Italian literature,” one whose life was widely seen to be “identified at many points with the course of Italian literature during the preceding half-century, and more especially with the intellectual interests of Southern Italy in its condition as a Spanish province.”[5] Manso introduced Milton to the Accademia degli Oziosi.