A application has been submitted to extend the Advanced Manufacturing and Research Centre Campus (AMRC) on the site of the old Sheffield Airport.
The centre is already home to a number of high technology companies, including a £110m Rolls Royce jet engine factory.
If approved, the new site would be developed over the next 10 years.
Located on the Rotherham and Sheffield border, the site closed to commercial flying in 2008, although it is still the base for South Yorkshire Police's helicopter.
The business park, which is home to a training centre and a nuclear research facility, opened in 2012.
A new £43m "flexible factory" is being built in a partnership between the University of Sheffield and companies including Boeing.
As well as new research facilities, offices and workspaces would be also be built.
James Newman, chairman of the Sheffield City Region Local Enterprise Partnership, said he hoped the expansion would encourage more businesses to invest in the area.
"They will be right in the nerve centre of advanced manufacturing," he said.
"All around them will be people doing top research in nuclear, in aerospace and in other high-tech industries."
"If we can bring high-tech jobs then that's what we want."

The Canadian-owned firm is Northern Ireland's biggest manufacturing employer
It employs around 5,000 people in its aerospace business.
The firm's Belfast vice-president Michael Ryan wrote in a letter to staff that the "European debate is very emotional".
The referendum will take place across the UK on Thursday, 23 June.
But, he said that Europe has been good to the company in terms of investment, air travel and giving free movement of goods.
The aerospace firm's Northern Ireland operation exports 95% of its products - 33% of them directly into Europe.
"There are strong views on either side," Mr Ryan wrote.
"But, I can only speak for our company's experience of operating within the EU and explain to you we believe it is better for our company that the UK remains within the EU."
He added that by clarifying the company's position it would "help" employees make "an informed decision on this very important issue".
While Bombardier has stated their support of staying in the EU, other businesses here support the campaign to leave.
William Wright, the founder of bus-maker Wrightbus which employs more than 1,500 people, said he was "totally in favour of getting out".

Researchers from the British Trust for Ornithology used data from a 12-year garden bird survey in their study.
This revealed that many blackcaps from Central Europe had shifted their winter migration, partly because of the supply of garden food in Britain.
The findings are published in the journal Global Change Biology.
"This is the first time that we've shown that feeding birds actually influences the distribution of a bird species across a whole country," lead researcher Dr Kate Plummer told BBC News.
The northern nightingale
Source: RSPB
Until the 1950s, there were hardly any records of blackcaps being in Britain in the winter, but in the past 60 years, researchers say, the number has increased "dramatically".
"We saw that both [climate change and garden feeding] were driving this shift in migration [from the Mediterranean to Britain]," Dr Plummer said.
"Where there was a reliable supply of food, blackcaps were more likely to be seen."
Throughout the 12 year period during which the observations were gathered - by more than 14,000 volunteers submitting a weekly record of the birds in their gardens - blackcaps became more strongly associated with garden food supply.
"So it looks like like they're evolving to adapt to using this big supply of winter food," said Dr Plummer.
Graham Madge, from the RSPB, told BBC News that it was only because "people take such a keen interest" and "monitor birds in these surveys, that we're able to understand the impacts we're having on birds and wildlife".
"It's positive news that blackcap numbers are increasing here, but when it comes to house sparrows and starlings, unfortunately [in these same surveys] we're seeing massive declines," he added.
As for the blackcap's preferred variety of feed - the birds appear to particularly like fats and sunflower hearts.
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Plans to expand a University of Sheffield research centre could create more than 1,800 new jobs, it has been claimed.
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The boss of Bombardier in Belfast has told its staff that "it is better for our company that the UK remains within the EU".
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Putting out birdfeed in Britain's gardens is shifting the migration of one particular winter visitor, the blackcap, scientists say.