More than two dozen people have been evacuated after a retail store on a shopping strip went up in flames, in a fire labelled 'suspicious'.

Fire crews responded to several calls reporting a two-storey building fire at Whitehorse Road in Nunawading in Melbourne's east about 2.20am on Sunday.

They arrived to find massive plumes of smoke coming from the blaze which had spread to an adjoining store.

About 25 to 30 people in nearby residences were evacuated and no one was injured, police said.

More than 95 firefighters and 26 trucks were deployed to fight the flames.

"The exact circumstances surrounding the fire are yet to be determined but at this stage it is being treated as suspicious," a police spokeswoman said.

A community advice alert has been issued for nearby communities, urging people to close windows and doors and turn off heating and cooling systems to avoid smoke entering their homes.

Whitehorse road remains blocked off in both directions.