The shooting happened around 3 pm on G and Santa Clara streets.
Fresno police say two men believed to be in their mid-30s were found with gunshot wounds.
They were both taken to a local hospital to have their injuries treated.
It is unknown if the two victims were staying at the Poverello House.
Officers say they are still searching for the suspect.
Authorities have not yet provided any details about what happened leading up to the shooting.