NHS Lothian said rises in its funding were not likely to keep pace with increasing demand for its services from an expanding elderly population.
The board, which said expenses were also going up as a result of developments in medical technology, said increasing productivity and efficiency alone would not be enough to bridge an annual £40m funding gap over the next 10 years and cuts in some areas would be necessary.
The organisation, which has an annual budget of £1.4 billion and is responsible for the health of about 800,000 people, is to take urgent action in identifying "areas for disinvestment" as it attempts to improve services at the same time as making substantial savings.
Buildings deemed unfit for purpose will be sold while the public will be encouraged to "take greater ownership" for their health needs and help in reducing avoidable demand on services.
Labour Lothians MSP Sarah Boyack called on the Scottish Government to state whether it would fund the health and social care services needed to cope with an increasing population on top of the rise in the number of elderly patients.
"NHS Lothian already struggles to meet national targets so we need to know what will go with the £400m savings and 'disinvestments' mentioned," she said.
In a document entitled Our Health, Our Care, Our Future, the health board also revealed plans to build a new regional cancer centre in Edinburgh, develop a new "care village" in the capital and eliminate bed blocking.
NHS Lothian chief executive Tim Davison said: "There is an increasing risk that unless we fundamentally change the way we work and organise our services, that the quality of patient care will deteriorate and we will fall short of meeting the needs and expectations of the population we are here to serve.
"We are proposing some bold steps to transform the way services are delivered to ensure they can keep up with modern-day demands and provide safe and effective care."