The incident occurred at around 6am when the robbers, dressed in dark clothes, wearing motorbike helmets and wielding handguns broke into the Chêne-Bougeries store, cantonal police said.
The gunmen entered the supermarket via the delivery entrance and threatened one of two employees on the premises, police said.
They then sequestered the employees for 30 minutes while they tried to open the safe, police said.
The men fled empty-handed.
No-one was injured in the incident, police said.
The Tribune de Genève reported that neither of the two employees — the head of the meat department and a stockist — knew the combination of the safe.
The robbers stole an iPhone from one of the employees which was found abandoned in a parking lot behind the Coop by a reporter of the newspaper, who turned it into police.
Police did not disclose how the gunman got away.
Meanwhile, cantonal police in Valais are looking for witnesses after a robber made off with an undisclosed sum of money from a Raiffeisen bank in Sion on Wednesday afternoon.
The man obtained the money by threatening an employee, before fleeing on foot,
Police are looking for a man aged 40 to 50 years old, 180 centimetres tall with a slender build.
He was wearing glasses, a dark wool cap with a visor, a red jacket with black shoulders and cape and blue overalls, according to the police description.
The suspect had a black sweater and work shoes with black gloves and may possibly have been carrying a dark-coloured bumbag.