Treasurer Josh Frydenberg believes Australia's health system will cope with a rise in coronavirus deaths and cases when the country reopens.
The Morrison government is applying sustained pressure to state governments considering backing away from nationally agreed vaccine targets.
Mr Frydenberg said Doherty Institute modelling guiding the plan out of the pandemic showed a zero-case aim was unrealistic.
"We have to learn to live with COVID," he told the Nine Network.
"It means deaths, it means serious illness and indeed means more cases. But our health system is built to cope. We have put in place a surge capacity for that."
He said there was no other alternative to opening up when it is safe to do so.
"We can't live in lockdown forever."
Under the agreement, the chances of lockdowns are reduced when 70 per cent of the population aged 16 and over is fully vaccinated.
At 80 per cent, only highly targeted lockdowns are likely to be used and state borders are expected to be open.
But premiers in WA and Queensland have called for updated advice because the initial modelling was based on relaxing restrictions with around 30 cases a day.
Doherty Institute director Sharon Lewin said the targets could be maintained with hundreds of daily cases.
Professor Lewin said the strategy relied on maintaining testing, tracing and isolation along with other public health measures at a 70 to 80 per cent full vaccination rate.
"We will be moving from a zero COVID goal to living with COVID and at lower manageable levels that don't overwhelm the healthcare system," she told Nine.
Prime Minister Scott Morrison will chair a national cabinet meeting of state and territory leaders on Friday with the deal fracturing.
The treasurer believes premiers and chief ministers are picking up on public sentiment supporting the plan.
Nine newspapers have published new polling showing 62 per cent of voters support the staged national reopening agreement.
Just 24 per cent support states and territories going their own way.
Labor leader Anthony Albanese said the opposition supported the plan after Mr Morrison accused him of undermining it.
"No one wants to see lockdowns there for one day more than necessary," Mr Albanese told the ABC.
"The reason why there are restrictions today is because the prime minister failed on those two fundamental jobs - quarantine and vaccines."
Australia has fully vaccinated 30.27 per cent of its population aged 16 and over and 52.78 have received one jab.
Victoria's stubborn coronavirus outbreak is persisting with another 45 new cases reported on Wednesday.
The situation continues to be dire in NSW which has a three-day average above 800 infections.
The ACT, which is the third jurisdiction in hard lockdown, detected a pandemic-high 30 cases on Tuesday.
Vaccine rollout coordinator Lieutenant General John Frewen is confident Australia will have enough supply to vaccinate children aged 12 to 15 if the rollout is expanded.
The Australian Technical Advisory Group on Immunisation is due to make a decision on that age bracket on Friday.
