According to latest polls, Donald Trump is losing in key battleground states after facing a slew of assault allegations.
However, Hillary Clinton remains unpopular with many voters and has faced more bad headlines about her use of a private email server.
Most Americans will cast their votes on November 8.
Millions are expected to tune into the third and final debate at the University of Las Vegas, Nevada, which gets under way at 09:00 EDT and will be moderated by Fox News journalist Chris Wallace.
Hillary Clinton and Donald Trump will discuss six topics: The debt and entitlements, immigration, the economy, the Supreme Court, foreign flashpoints and their fitness to be president.
The Republican presidential candidate has faced damaging fallout after a video emerged of him making inappropriate comments about groping women, with senior Republicans deserting him.
In recent days Donald Trump has railed against the election process itself, warning the vote is “absolutely rigged” with “large-scale voter fraud” taking place.
The New York billionaire’s remarks prompted a scathing response from President Barack Obama, who said the Republican challenger should “stop whining”.
Donald Trump has invited Barack Obama’s estranged half-brother, Malik Obama – one of his supporters – as a guest.
He also invited Patricia Smith, whose son was killed in an attack on the US diplomatic mission in Benghazi, Libya, in 2012, while Hillary Clinton was US secretary of state.
In contrast to Donald Trump, Hillary Clinton has kept a low profile ahead of the debate to prepare for the showdown.
Hillary Clinton’s spokesman said the Democratic nominee was ready for whatever “scorched-earth” tactics her rival might try.
She is likely to face questions about a batch of hacked emails from the account of her campaign boss, released by WikiLeaks, that Donald Trump has seized on.
Before the last debate, Donald Trump appeared at a news conference with women who accused Bill Clinton of s**ual misconduct. Since then he has suggested Hillary Clinton took performance-enhancing drugs ahead of that meeting.
Hillary Clinton’s campaign has signaled their candidate will try to focus on policy.
Among her guests, Hillary Clinton is bringing Donald Trump critic Mark Cuban, as well as Hewlett Packard Enterprise CEO Meg Whitman, one of her highest-profile Republican backers.
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