The Mass will be held outside the Philadelphia Museum of Art in centre of the city.
It's part of Pope Francis' first trip to the US since he became Pope two years ago, and he will also be addressing Congress in Washington D.C, and visiting New York and Cuba during the week.
His appearance needs around 10,000 volunteers to help and the Holy Father is expected to arrive around September 26th for the World Meeting of Families conference, looking a Catholic family life.
The finalised schedule for the visit has not been announced yet.
The last time a Pope visited the city was Pope John Paul II in 1979.
Mark Ross, regional manager of emergency preparedness for the Hospital and Health System Association of Pennsylvania, said all hospitals in the local area can have special meetings to plan for the visit.
Preparation includes stocking up on medical supplies and having staff sleep in the hospitals as travel may be difficult.
Mark Ross said: "This whole region is going to see a couple million visitors.
"I think we are all going to be impacted. It is a great thing for the entire region," he told USA Today.
Two Christians in the area have even created a "Pop Up Pope" to spread word about the visit.
Paul Tanner and Christa Scalies are behind the cardboard cut-out idea. Mr Tanner said: "We are so close - and it is a once-in-a-lifetime opportunity.
"How could you miss that? Especially being Catholic."
Christa Scalies said forward planning is key: "I think people are going to be kicking themselves come September, if they don't plan it out now."
