Experts predict it could cost up to £2bn to provide alternative habitats for wildlife if a proposed Thames Estuary airport is built.
An estuary airport on the Isle of Grain has been proposed by London Mayor Boris Johnson.
The report published by the Airports Commission said it would "radically and irreversibly" change the landscape, which is "noted for its remoteness".
The report said impact studies lasting many years would be needed.
The environmental impacts study said an airport development was likely to result in "adverse effects" on international nature conservation sites, including the Thames Estuary Marshes special protection area.
The report said: "An airport would need to demonstrate that there are no feasible alternatives.
"A large area of compensation habitat creation would be required and this would be on a scale unprecedented for any single development in Europe."
Based on other projects, the estimated cost would be between £70,0000 and £100,000 per hectare, the study found. This would result in a cost of between £149m and £2bn, if the airport was to be built.
Areas on the east coast in Essex and Suffolk could be considered, but there was a "high level of uncertainty" they would be suitable.
"Further extensive studies would be needed over a large area and over many years," the report said.
The proposals have faced opposition from councillors and MPs in Kent and Medway.
Rehman Chishti, Conservative MP for Gillingham and Rainham, said: "This new report confirms everything that we in Medway have been saying - the local authority, the residents - that the idea of having an airport in the estuary will have huge environmental implications for the South East and also for the area locally, and is unsustainable."
Val Shawcross, the Labour spokeswoman in the London Assembly, said: "The idea of a Thames Estuary airport has long been dead in the water, but if a final nail in the coffin was needed, this is surely it.
"Boris [Johnson] has wasted millions of pounds on this vanity project.
"With this latest report in mind, he needs to accept that the evidence is now totally against him and that no more public money should be spent pursuing a Thames Estuary airport."
The Green Party called for a reduction in air traffic rather than building a new airport.
Darren Johnson, a Green Party member on the London Assembly, said: "The Airport's Commission has confirmed what a costly environmental disaster the mayor's Thames Estuary airport represents.
"The mayor needs to abandon this ill-conceived project."
But Daniel Moylan, the mayor of London's chief advisor on aviation, said: "Few large scale infrastructure projects avoid significant costs for environmental considerations, but our estimate is that the cost of providing new habitat would be £500m, a quarter of that quoted by the Airports Commission.
"More importantly, their report confirms that every environmental objection can be answered, every obstacle can be overcome and there is nothing in the evidence published that should prevent the estuary option being shortlisted in September.
"Couple that with an estimated £7bn of economic benefit every year, and the hundreds of thousands of jobs that would result from moving Heathrow to the Thames Estuary, and the Airports Commission can have no alternative but to include the estuary option on its formal shortlist."
The report is the first of four due to be published this week, looking into different aspects of the feasibility of a Thames Estuary airport.