The shooting happened at about 1:45 p.m. in a building in the 2900 block of East 78th Street in the South Shore neighborhood.
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WATCH: Police provide update after deadly South Shore shooting
Police provide update after 5 shot, 2 killed on South Side
Monay Mack, man who lives around the corner, said this is normally a quiet block.
"This is not normal. I'm very surprised. Five people, two fatals. I'm shocked," Mack said. "I'm surprised about that. Normally, I walk this block every morning to go down to the beach... and you never hear anything happening over here. But, down the street, there's quite a bit of activity goes on down there."
Two victims were found dead inside a second-floor apartment, and two others were transported to the University of Chicago Medical Center in critical condition, police said. A fifth victim fled the shooting and ended up at a McDonald's about a half a mile away East near 79th Street and South Yates Boulevard.
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During a press conference, police called the incident a "targeted home invasion," but declined to offer a possible motive.
"I can't discuss a motive as it's unique to the crime itself, and I don't want to take that away from the area detectives. What I can say, specifically, is it does not appear to be a random act," said CPD Deputy Chief Sean Loughran. "We're investigating any relationship between any victims and offenders at this time, but it is very, very preliminary to discuss it."
Police have also declined to give the ages and genders of the victims, but said they are looking for multiple offenders.
SEE ALSO | 13-year-old boy wounded in Chicago shooting on South Side: CPD
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Investigators have been canvassing the area, seeking eyewitnesses and looking for surveillance video.
"The crime scene, of course, will be taking pictures, video, as well as recovering any specific evidence from the scene that would link these offender or offenders to this heinous crime," Loughran said.
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This is a developing story. Check back with ABC7 for updates.
ABC7 Chicago contributed to this report.