The fire broke out at a store on Whitehorse Road at Nunawading before spreading to an adjoining building about 2.30am today.
More than 100 firefighters were called to the scene and an aerial fire truck was required to contain the blaze.
Victoria Police evacuated 25 to 30 nearby residents and paramedics attended the scene.
There were no reported injuries.
An alert was issued for large volumes of smoke in the area travelling in a southwest direction.
Police said the fire is being treated as suspicious and an investigation has been launched.
Anyone who witnessed the incident, has dashcam/CCTV footage or information is urged to contact Crime Stoppers on 1800 333.