A Beechcraft B200 Super King Air carrying a pilot and four passengers may have suffered "catastrophic engine failure" soon after takeoff from Essendon Airport about 9am.

The plane appeared to veer left, before crashing into the roof of the Essendon DFO shopping centre and bursting into flames, killing all five people on board.

Within 24 hours, crash investigators had already identified "several factors" of interest, Australian Transport Safety Bureau's chief commissioner Greg Hood said.

"With any accident, particularly aviation accidents, we find that initially there are several factors that leap out at you," Mr Hood told reporters on Wednesday.

"The investigators are trained not to put any bias on what is the obvious.

"So whilst in the initial walk-through [on Tuesday], the initial examination of records, we have discovered some interesting facets, we really need to gather all the evidence and conduct the analysis before we can say what caused the accident."

Mr Hood confirmed the plane was designed to be able to take off safely, even with one engine damaged.

The pilot, Max Quartermain, was able to make two mayday calls to air-traffic control before impact.

But Mr Hood said those calls only consisted of the word "mayday" and did not contain information about the cause of the crash.

Fairfax Media revealed Mr Quartermain was the subject of a long-delayed ATSB investigation over a safety incident while flying a similar model of plane in 2015.

Mr Hood said he was unaware of the pilot's previous history, and refused to answer questions about why the investigation has not yet been completed, nor whether Mr Quartermain, 63, was safe to fly.

"I realise there is a lot of speculation," Mr Hood said.

"As Australia's no-blame transport safety investigator, we won't be engaging in any speculation.

"It is our undertaking to produce a public, preliminary report in 28 days."

Police say they have more than 100 witnesses still to interview.

Essendon Airport will reopen on Thursday, but the DFO will remain shut indefinitely.

Victoria Police are working to prepare a brief for the coroner, and expect a coronial hearing to be held.

The Beechcraft has been described by veteran aviators as an "iconic" aircraft, with thousands in operation about the world.

The crash has reignited concerns among the local community about building houses and shops so close to a busy airport.

Essendon Fields chief executive Chris Cowan said the airport had an "enviable safety record".

"Airports and cities mix, that's a reality of modern day life."

He said airport development had been rigorously planned, and there was no case to be made for moving the DFO.

"There are 6000 jobs here [at the airport]. There has been very strong local support," Mr Cowan said.

"[Tuesday] is obviously going to have some impact on that, and that's something we're going to work closely with the community on."

In the airport's main thoroughfare an Australian flag was flying at half-mast on Wednesday.