Someone called 911 at 12:13 p.m. to report the shooting, which happened in the 2900 block of Westboro Drive, a residential street lined with single-family homes.
Officers arrived to find a man who had been shot at least once. The victim was pronounced dead at the scene at about 12:25 p.m.
Investigators are still looking for the shooter, who they believe is a man who fled in a white vehicle afterward, police Sgt. Jason Dwyer said.
Dwyer said police do not know the relationship between the suspect and the victim. He said it appears there were other people in the house at the time of the shooting.
There is no indication the shooting was gang-related, Dwyer said.
"We do believe that the suspect is armed and dangerous," he said.
The killing marks San Jose's 14th homicide this year.
As of about 2 p.m., Westboro Drive remained blocked off as police continued to investigate.