Prime Minister Giorgia Meloni's right-wing government gave its final approval for the bridge over the Strait of Messina on Wednesday, earmarking 13.5 billion euros ($A24.2 billion) for a project that has been under discussion for more than 50 years.
"They could offer me three times the value of my house, but that doesn't matter to me. What matters is the landscape. They must not touch the Strait of Messina," said Mariolina De Francesco, a 75-year-old living in the Sicilian city of Messina.
More than 440 properties will have to be expropriated on the Sicilian side and in the Calabria region on the mainland to make way for the 3.7km bridge and connecting roads and railways.
"Our lawyers will take action, and we will stop them. That's guaranteed," said De Francesco, whose house lies near the site of one of the bridge's planned 399m land towers.
Infrastructure Minister Matteo Salvini said preliminary works should start in September-October, and has promised generous compensation to those required to surrender their property. The bridge is due for completion in 2032.
The Messina Strait Company overseeing the project is bracing for a big legal fight.
"(Legal appeals) certainly keep me busy because they waste a lot of our time," its CEO Pietro Ciucci told La Stampa newspaper.
Environmental groups this week filed a complaint with the European Union, flagging serious risks for the local ecosystem.
The Torre Faro district, on the northern edge of Messina, includes a nature reserve surrounding two ponds, and Calabria appears within arm's reach when strolling along the seafront.
Committees of 'No Bridge' residents say the area's environmental value and seismic risk make it unsuitable for the infrastructure. They also fear the works will drag on, making the neighbourhood unliveable because of the noise.
The Messina Strait Company says the bridge will be designed to withstand very strong earthquakes and will not be placed on active fault lines. It has also promised mitigation measures to safeguard habitats and protected species.
Contractual obligations will ensure that the timing and effects of construction activity, including noise, will be kept under strict control, the company added.
Authorities have pledged strong safeguards against any mafia involvement. The two regions are home to the Cosa Nostra and 'Ndrangheta mafia organisations, which have a long history of infiltrating lucrative public works projects. The government is also considering whether to categorise investment in the bridge as defence spending, which would help Italy meet new NATO targets to boost military budgets.
House expropriations are set to proceed gradually, in line with construction progress.
Activists and lawyers estimate some 1000 people could lose their homes, and say the increased costs since the project was first awarded may breach European Union public procurement laws.
"We are a country governed by the rule of law within the EU, so even the government must respect the rules," said Antonio Saitta, a lawyer representing some Messina residents.
Saitta said the main way of blocking the bridge was to file an appeal with an administrative court against the government's decision by the end of October.