The city expects an extra two million visitors and hotel capacity to be over 90% for the U.N. General Assembly and papal visit.
Mom -and-pops near where the pope plans to visit say they are worried the blocked streets and security will hurt their bottom line, but nonetheless plan to remain open.
"It could be a disaster," said Steve Millington, the general manager at Michael's on East 55th Street. "I think it will make deliveries much more difficult."
Ron Warren, the director of the Mary Boone Gallery at 745 Fifth Ave., said he expects "less people, because people are not going to be able to get there."
This isn't the first time New York has faced a week like this, of course.
Andrew Riggie, the executive director of the NYC Hospitality Alliance, said members can draw on past experiences to mitigate potential losses.
"There's a lot of excitement around the pope's visit. Some restaurants benefit from increased business and some lose business due to the barricades and security measures, but this is just a reality of running a restaurant in New York City," he said in a statement.
Jim Albert, security chief at 34th Street Partnership, said the stores around Madison Square Garden are concerned about the logistics because of the street closures but they are all excited to be part of the historical visit.
"They're open during the blackout and storms. I'm sure they will open when the pope comes," he said.