The pair were in Mount Druitt in western Sydney about 7.45pm on Thursday when they were struck on a busy arterial.
Emergency services arrived to find the toddler's caregiver - a man aged 57 - severely injured and were unable to save his life.
Shortly after, a man believed to be the toddler's father presented the boy to hospital.
He was rushed to Westmead Children's Hospital in a critical condition.
The driver involved in the crash, a woman aged 37, was taken to hospital for mandatory testing and was assisting with inquiries, police said on Friday.
Anyone with dashcam footage is asked to pass it to police.
In a separate fatal crash overnight, an e-bike rider died after he collided with a police car about 3am.
Police say officers had been trying to pull the rider - a man aged in his 40s - over when the crash occurred in Waterloo.
The man was treated by paramedics but died at the scene.
Officers from outside the command area will launch a critical incident investigation into the crash and the police actions.
That investigation will overseen by the police watchdog.
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