The NHS must save up to £10bn a year by 2020 by slashing agency staff, selling off land and reducing drug errors, the Health Secretary is expected to warn.
Jeremy Hunt, who is set to speak at The King's Fund annual conference in London, will tell delegates that NHS managers will have to "rethink" how they spend money.
"If we are to be truly financially sustainable we need to rethink how we spend money in a much more fundamental way," Hunt is expected to say.
The proposed reductions from the NHS' annual budget of £113bn ($178bn, €143bn) will be helped by a drive for more innovation, according to Hunt.
"We have not built a system that is good at adopting and rapidly diffusing new ways of doing things," the heath secretary is expected to say.
"Given that much innovation saves money as well as lives, we need to change the NHS from a lumberingly slow adopter of new technology to a world class showcase of what innovation can achieve."
Hunt will also say that reducing prescription errors could save £551m, better acquisition of services and goods could also deliver £1.5bn of savings and reducing the service's £2.6bn spend on temporary staff will make savings.
The Health Secretary is also expect to suggest that NHS trusts should sell off "surplus land and estates".
Andy Burnham, Labour's Shadow Health Secretary said: "The hypocrisy of Hunt gets worse by the day."
"He slashed nurse training places and left hospitals at the mercy of expensive agencies and overseas recruitment. He should put his own house in order first.
"David Cameron spent more than £1bn on pay-offs for NHS managers during the re-organisation – a scandalous waste of money when patient care is heading backwards."