Coalition parties have conceded holding onto the seat of Farrer will be a tall order ahead of the crucial by-election.
Voters will head to the polls on Saturday to replace former opposition leader Sussan Ley in federal parliament, following her resignation.
While the electorate has been held by coalition parties since the seat's creation in 1949, the contest is looming as a showdown between One Nation's David Farley and independent Michelle Milthorpe.
Should One Nation win, it will be the first time the minor party has taken a seat in the lower house at an election, while Ms Milthorpe is seeking to win after coming close to unseating Ms Ley at the 2025 poll.
Deputy Liberal leader Jane Hume said a win for the party in the seat would be difficult.
"We know it's a tough ask, when a long-serving local member retires, a by-election is always difficult," she told ABC Radio on Friday.
"We'll be fighting for every single vote, not taking anyone for granted."
Senator Hume warned against voters turning anger for the Labor government into a protest vote against the major parties and going with One Nation.
"The good folks of Farrer definitely know that they're angry at the Albanese government," she said.
"They're beginning to understand that a vote for One Nation will simply entrench the Albanese government, and a vote for teal will simply mean that you get Greens politics."
Nationals leader Matt Canavan also admitted reclaiming Farrer for the junior coalition party would be a struggle.
"There's no doubt it's an uphill battle for us, it's a real challenge," he told ABC Radio.
One Nation leader Pauline Hanson said she was confident ahead of Saturday's poll.
"(Mr Farley) is going to be very beneficial on the floor of parliament, working with Barnaby Joyce ... we're going to have such a voice," she told Sky News.
"It's going to put a clear message to all those other people out there. A vote for One Nation is not a waste of a vote."
The comments came after a video emerged of Liberal senator James Paterson in a scuffle outside a pre-poll centre in Albury with a One Nation volunteer.
The Liberals have been running campaign ads on Mr Farley's political past in Farrer following revelations he had previously tried to run for Labor.
But Senator Hanson said Mr Farley had not been a member of Labor.
"Regardless of it, everyone out there who's voting this election, a lot of people never voted for One Nation before. They've been associated with some other political party before One Nation," she said.
"I'm sick of the dirty games constantly being directed at One Nation all the time because they know they're losing their support. They know they're losing the votes and they can't handle it."
As of Wednesday, 36,000 people had voted early in Farrer with the Australian Electoral Commission also receiving 9000 postal votes.
