As a performer, he plays concerts as soloist, in chamber music ensembles, in orchestras, and with different choirs in several venues in Europe and the US with a vast repertoire spanning from Frescobaldi to contemporary composers. In May 2020 he recorded the complete set of Etudes Op. 23 by the contemporary Italian composer Giovanni Albini. Matteo Generani is currently devolving great effort in the research, revival, and study of Giuseppe Martucci’s output (Martucci Research). In December 2024, Matteo's CD on Martucci Solo Piano Works was released with the Naxos Recording Label.

In conjunction with performing, Matteo Generani is also passionate about teaching. He worked as a piano instructor for the Cultural Association Tetracordo, and the Ricordi Music School, Opera–Milan in Italy, he taught piano group classes at Central Michigan University, and as one of the piano faculty at the University of Missouri–Kansas City (UMKC) Conservatory Academy.

Matteo Generani is also interested in outreach initiatives. He actively participated in the “Emerald Coast Music Alliance Festival” and “Music for All,” two outreach programs that brings exposure of world-class classical music performances to populations who would otherwise not have access to such. Matteo is also co-artistic director of Classical Music Express.

Matteo Generai has performed for several Lyric Opera of Kansas City events in past seasons, and was the Resident Artist Coach-Accompanist for the 2024–2025 season. This season at Lyric Opera, he will play on the mainstage with the Kansas City Symphony for The Brightness of Light with Renée Fleming and Rod Gilfry, The Barber of Seville, and Turandot, as well as in the pit for the world premiere of Lori Laitman's Maya and the Magic Ring.

He is the co-founder of the Medhelan Duo and the Neo-Art Piano Duo.