The around £2bn development is among the projects included in the Government's New Hospital Programme.
Professor Julian Redhead, chief executive of Imperial College Healthcare NHS Trust, said: ‘St Mary's has an extraordinary history of care and medical breakthroughs across nearly 200 years, from the discovery of penicillin to becoming one of the country's first major trauma centres. But much of our estate is now very old and increasingly difficult to maintain, with building failures an increasingly regular occurrence despite spending millions every year on essential maintenance.'
The new plans, which are open to public consultation, come as the trust works towards submitting a planning application for the whole site in spring 2027.
The site includes the expansion of Paddington Life Sciences, the hospital's partnership with pharmaceutical, clinical device, research trials and technology businesses that have made their home in Paddington Basin.
Independent evaluation has shown the campus could help create between 9,000 and 11,000 additional jobs and generate up to £1.3bn more per year in economic activity.
The plans have been produced by a team of leading industry experts working with the trust, including development managers Stanhope Plc, masterplan architects Allies and Morrison and hospital design architects HOK, alongside Gillespies, Savills and LCA.
