The event which is being held in the main audience hall is being seen as the latest in a line of decisions by Pope Francis to reach out to the hundreds of nearby rough sleepers.
The concert is being organised by Monsignor Konrad Krajewski, one of the pontiff's assistants who has specific responsibilities for the homeless. He's been in charge of the installation of wash rooms in St Peter's Square which allow rough sleepers a place to shower.
Those attending the event won't be charged but will be given envelopes to leave donations for the poor.
The Vatican says it will feature a mix of symphonic music, Gregorian chant and hard rock.
Pope Francis has released a message to organisers and sponsors in which he thanks them for all they've done.
"Music has the capacity to unite souls and to unite us to the Lord," he said.
"It is horizontal but also vertical, soaring high, and it liberates us from anxiety. Even sad music - we think of those slow laments - even these help us in difficult moments.
"I thank you very much, because a little spirit will do much good to all in the ever-present materiality which brings us down and destroys our joy.
"As believers, we have the joy of a Father who loves us all and the joy to be able to be brothers to all. However, you will re-seed this joy with this concert.
"It will be a concert to seed joy, not a passing happiness, no: the seed will remain there in the souls of all and will do much good for all. I thank you again for all the good that you do; thank you from the heart."