The scheme has been put forward by landowner Guy's and St Thomas' Foundation with development partner Stanhope. Allford Hall Monaghan Morris are the lead architects.
The proposal includes office and 'lab-enabled' space for life sciences and med-tech use, 133 homes and various retail, cultural and community spaces.
It's 12 years since the foundation abandoned its last attempt to develop the site, then known as the Founders Place scheme.
Since the failure of the last scheme in 2010 the foundation has expanded its options by buying back the head lease of the Becket House office building on Lambeth Palace Road.
The rest of the land north of Royal Street is currently occupied by two blocks of flats called Canterbury House and Stangate. The protected long-term tenants of these blocks have been rehoused by the foundation in recent years and the current occupants are all on short-term tenancies.
The land to the south includes the temporary Oasis Farm Waterloo, the former Holy Trinity School – latterly a Tibetan Buddhist centre more recently branded as Old Paradise Yard – and a car park which has been undeveloped since the demolition of Blitz-damaged Holy Trinity church in 1954.
More than 37,000 people have signed a 'Save Waterloo Paradise' petition urging Lambeth councillors to reject the scheme.
Objectors to the planning application include Historic England, the Twentieth Century Society, London Historic Parks and Gardens, the City of Westminster and the International Council on Monuments and Sites (ICOMOS).
Heritage bodies are concerned that the scheme will affect the setting of the Palace of Westminster's Elizabeth Tower when viewed from Parliament Square.
Local resident Matthew Demwell - one of the coordinators of the 'Save Waterloo Paradise' campaign - addressed the meeting. He suggested that the developers had over-emphasised the med-tech element of the scheme, when only a quarter of the proposed office space would be 'lab-enabled'.
He added: "Old Paradise Yard is unique and quirky. Any inner-London borough would love to have it. It inspires innovation, creativity and community engagement.
"It is irreplaceable, along with its historic Victorian school buildings."
Mr Demwell went on to describe the impact of the development on Archbishop's Park. "The effect would be dehumanising," he said.
Another objector's words were read out by a council officer, including the observation that the scheme only includes a net increase of four homes (129 homes will be demolished and 133 will be constructed).
Michael Ball of Waterloo Community Development Group warned that if approved, the development would be likely to be 'called in' by central Government for a public inquiry, and if turned down, would lead to an appeal.
Instead he urged the council to seek a more modest development that could win the support of a wider range of local people and groups.
Kieran Boyle, chief executive of Guy's and St Thomas' Foundation said: "The Royal Street development is critical to improving health and wellbeing.
"It's a well-connected site at the centre of an existing life sciences and healthcare ecosystem."
Mr Boyle noted that Guy's and St Thomas' NHS Foundation Trust hoped to occupy some of the space in the new development.
David Bray, development director at Stanhope, said that the project would "provide a major boost for Lambeth's post-covid recovery".
He added: "These proposals will make a real improvement to visiting, working and living in the north of the borough. We hope that committee members will support our plans for Royal Street."
Summing up, planning applications committee chair Cllr Joanne Simpson said: "I give huge weight to the creation of the bio-tech hub and the lab-enabled space, making this a destination that is almost international in its prominence and importance.
"I think the resulting consequences for Lambeth residents will be monumental."
The application won the unanimous backing of the four councillors present at the meeting.