Cops released a surveillance video that they said showed the interaction between the man and the woman on the block. No arrest had been made as of last night.
The man was described as Hispanic, 25 to 30 years old, about 5 feet 7 and wearing a black T-shirt and blue jeans with a baseball cap and a messenger bag.
Ashley Lu, 25, who lives on the block, said she was standing in line at a nearby 7-Eleven when she overheard someone talking about the crime.
"It's surprising," Lu said. "You expect to be OK - even if it's late - in an area like this."
According to one real-estate website, homes on the block are listed at $500,000 to $700,000.
"These [criminals] aren't a part of the neighborhood," said Carlisle Frank, who used to live on Spruce Street near 22nd and now lives in Chestnut Hill. "I guess they prey on people because people think it's safe. It's not."
According to the Megan's Law website, 47 nonincarcerated registered sex offenders live within a half-mile radius of the block.
And the reported rape summoned plenty of bad memories for neighbors who recall the crimes of Troy Graves, the so-called "Center City Rapist," now serving a life sentence for sexually assaulting six women from 1997 to 1999.
Among his victims was Shannon Schieber, who was raped and murdered in her home on 23rd Street near Manning on May 7, 1998.
Yesterday, a 46-year-old woman who lives next door to Schieber's former residence said she considers the neighborhood safe.
"I've done town watch for years," said the woman, who asked not to be identified. "But you always have to be on guard."
But Lisa Jones, 44, who lives in Center City, said the latest rape had left her shaken, feeling that it "could have been me."
Jones, who is a doctor, said it was around the time that the Center City Rapist was on the loose that she decided she wouldn't walk home alone at night anymore.
"I usually go running at 6 a.m.," Jones said. "I'll wait to do that now."
On Twitter: @PatriciaMadej