The 28-year-old was found in a critical condition at Narcissus Avenue in Quakers Hill about 8.30pm on Friday.
Paramedics worked to save the man but he died en route to hospital.
Detectives probing the incident have asked anyone with CCTV footage, dashcam or information about what happened to come forward.
A crime scene has been set up at the residential street.
Meanwhile, a teenage boy died following a stabbing in the state's west overnight.
Emergency services were called to a home on Nymagee Street, Narromine at 9pm on Friday following reports of a stabbing.
Officers arrived to find a 16-year-old boy with stab injuries to his neck.
He was treated at the scene by NSW Ambulance paramedics before being taken to Dubbo airport where he died.
Following inquiries, police arrested a 26-year-old man at a home nearby.
Police have established a crime scene and detectives have launched an investigation into the incident.