Firefighters found the two-story home engulfed in flames when they arrived around 5:25 a.m. Saturday.
They forced their way inside and found the man - identified only as a city resident in his 60's - and took him to University Hospital, where he later died.
Prosecutor's spokeswoman Katherine Carter says the man had a single stab wound to the chest. She said he had been evicted from the home on Friday.
It wasn't immediately clear how the fire was started, but investigators say it appeared to have multiple points of origin.
The home was severely damaged but not destroyed.