Helene Pastor, 77, said to be close to Monaco's royal family, and nicknamed the "vice princess", had been visiting her son in hospital when an unknown gunman opened fire on her Lancia Voyager car.
The attack has baffled detectives. Pastor's chauffeur was seriously injured in the attack and died four days later. Pastor was taken to hospital with injuries to her face, neck, chest and abdomen, but died on Wednesday.
She had spent two hours before the attack at the bedside of her son Gildo, who had suffered a stroke, and left the Archet hospital in the west of Nice in the early evening. As her car pulled out of the hospital on to the main road, a man leaped out from behind a parapet wielding a sawn-off shotgun and fired into the passenger side.
After shooting a first time, the killer leaned into the slowly moving car and shot a second time, critically injuring driver Mohamed Darwich, 64, who had worked for Pastor for 15 years. CCTV images show the attacker running off with a second man. The car continued a further 20 metres before crashing into a parked vehicle.
"Unfortunately, the images are not perfect and until now we haven't been able to identify the murderers, who were disguised," said a police spokesman.
A report in the French daily Le Figaro said investigators suspected the two were members of Italy's most notorious organised crime gangs - either 'Ndrangheta or the Camorra. Both clans are said to have gained a strong foothold in the French Riviera's property sector, in which the Pastor family are key players.
Pastor, the sister of Michel Pastor, the former chairman of Monaco football club who died in February, was described by shocked friends as a "model of wisdom and discretion".
The Pastor family has a huge portfolio of property and land in Monaco estimated at 50,000 sq metres, or 2.5 per cent of the principality's area.
The holdings are part of a building dynasty established by Helene Pastor's grandfather, Jean-Baptiste, an Italian immigrant stonemason from a poor family in Liguria, who arrived in Monaco in the 19th century. After building Monaco's first soccer stadium, the firm was taken over by his son Gildo, who bought up swathes of seafront real estate at bargain prices after the second world war. When he died in 1990 his three children, Helene and her late brothers, Michel and Victor, inherited his fortune.
The three branches of the Pastor family are believed to own between 3,000-4,000 flats of a total of 20,000 in the 200-hectare principality. The family's flats are worth an estimated €20 billion (HK$212 billion). They are also friends of Monaco's royal family.
After the attack, Prince Albert said he was "deeply upset" and offered the Pastor family his "very deep support".
Police, who first described the attack on Pastor's car as an "ambush" and an "attempted execution", admitted they had no idea whether it was Pastor or her chauffeur who was the target of the gunmen, and said the choice of weapons did not suggest a professional assassin or the mafia.
"All lines of inquiry remain open," a police source working on the murders told Le Nouvel Observateur magazine.
"The inspectors of the Nice criminal division are examining the weapon, which is not a favourite of the big professional bandits."
Police say they are now looking into any family secrets that may have provided a motive for Helene Pastor's murder.