The Liberals have declared victory in the Nepean by-election, which is seen as a preview of what to expect when the rest of Victoria hits the polls in November.

Candidate Anthony Marsh celebrated with state Liberal leader Jess Wilson on Saturday evening. 

'It's been a hard fought campaign. It's a result we were hoping for, and I'm so glad I could bring it home for you tonight,' he said.

He told crowds he would be in the party room on Tuesday, 'fighting for the people of Nepean as we lead into one of the most important state elections that we've seen'.

Wilson also addressed the room, describing how Marsh had 'worked tirelessly every single day' to listen to the residents on the peninsula.

'He and his wife, Nat, are raising their young family on the peninsula,' she said.

'They are invested in the future, and I know how passionate he is about fighting for residents down here on the peninsula.'

After poll booths closed on Saturday, results around 7.30pm showed Marsh ahead on 36.6 per cent with just under 22 per cent of primary votes counted.

Marsh was followed by community independent Tracee Hutchison on 23.8 per cent and One Nation's Darren Hercus on 21.2 per cent.

On a two-candidate preferred basis Marsh was on 55.4 per cent and Hutchison on 44.6 per cent. Labor opted not to field a candidate in the by-election.

Saturday's by-election was triggered by the sudden resignation of Victorian Liberal deputy leader Sam Groth in January, with the party holding the seat since its inception for all but four years when it fell to Labor.

Marsh was forced to admit he didn't live in the electorate and therefore was unable to vote for himself on Saturday, but said he had been mayor in the area three times over the past five years.

Hercus told reporters it was a tight race with a mixed response from voters frustrated by empty promises.

'We've had a few Liberal voters come over to us for frustrations they've been feeling with their own party,' he said.

One Nation leader Pauline Hanson had campaigned alongside Hercus but was absent on polling day.

'People will vote for her rather than me,' Hercus said.

Hutchison told reporters many voters were looking for an alternative as the area had been overlooked and let down by the major parties for decades.

'I am putting myself forward as someone who is of this place, who cares deeply about this place,' she said.

A strong One Nation showing would have backed up national polling and the South Australian election result, and bode ill for the Liberals in the Victorian state election, senior politics lecturer at Monash University Benjamin Moffitt said.

'If they even do somewhat well in Nepean, that's a real problem for the Liberal Party,' Dr Moffitt said.

Total voter enrolment at close of rolls was 50,910.

The electorate takes in the wealthy postcodes of Sorrento, Portsea and Flinders, and low socio-economic areas such as Capel Sound, formerly known as Rosebud West.

The Mornington Peninsula is officially part of metropolitan Melbourne, but lacks comparable services, with public transport and a planned revamp of Rosebud Hospital among key issues for locals.