West St Convenience Store in Hadfield was significantly damaged in the targeted attack about 3.30am today.
Detectives are investigating whether the incident is linked to a series of arson attacks targeting tobacco stories across the state.
Police believe the fire was targeted, and officers are treating the incident as suspicious.
A crime scene has been established, while an arson chemist along with detectives investigate the scene.
A blue kerosene bottle left at the scene has also been the focus for investigators.
The store was targeted in another arson attack on August 30. It's located just two kilometres from Hadfield Finest Fruit and Veg, which has also been targeted by fire in the recent months.
At least 28 tobacco stores across Melbourne have been partly destroyed by arsonists as disputes involving Middle Eastern crime groups escalate.
Victoria Police established a new task force earlier this month to focus on arson attacks, extortion and firearm incidents.
Anyone who witnessed the incident or with dashcam footage is urged to contact Crime Stoppers on 1800 333 000.
