The victim was found inside a silver car on Metchley Lane, close to Queen Elizabeth Hospital in Birmingham, about 3pm today.
The man was already being treated by paramedics by the time cops arrived on the scene.
He was taken to hospital where he was later pronounced dead.
Officers would like to hear from anyone who may saw a man running from the car after the incident.
Information is also being sought from drivers in the area who witnessed a silver car driving erratically from Harborne Lane before the crash.
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A West Midlands Police spokesperson said: “We’ve launched a murder investigation this afternoon following the death of a man who was found with a stab wound.
“He was found in a car which had crashed in Metchley Lane, Birmingham, at just after 3 pm this afternoon.
The statement continued: “Officers attended and found the man being treated by paramedics but sadly despite their efforts he was later pronounced dead at hospital.
“We’re keen to hear from anyone who may have seen the car, which was silver, driving erratically from the direction of Harborne Lane prior to the crash.
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“We’re also keen to trace a man seen running from the car, as he may have vital information to help the investigation.”
Roads in the area are cordoned off as enquiries are made.
Anyone with information is urged to contact police, quoting log 2423 of September 22.