Al Jazeera's Rob Reynolds in Nashville said McCain was likely to be more aggressive than he had been in the previous debate in Oxford, Mississippi.
McCain's campaign has unleashed a number of attacks on Obama in the last few days as his advisers signalled they wanted to move the debate away from the economy.
The Arizona senator and Sarah Palin, his running mate, have criticised Obama for his links to William Ayers, a member of the Weather Underground radical group in the 1960s, and his former minister, Reverend Jeremiah Wright.
Obama has responded by raising questions about McCain's relationship with Charles Keating, a central figure in the US "savings and loan" scandal in the late 1980s and early 1990s that cost taxpayers billions of dollars.
McCain was criticised by a US senate committee for his "poor judgement" over the scandal.
The change in tone during the campaign has raised expectations for an explosive debate.
"In order to change the dynamics of this race, we anticipate that McCain will launch his nastiest attacks and continue to lie about Barack Obama's record," Bill Burton, an Obama spokesman, said.
A McCain supporter asked the him on Monday "when are you going to take the gloves off?"
McCain replied with a grin: "How about Tuesday night?"
Obama surges ahead
Polls judged Obama the winner of the first debate two weeks ago, but Tuesday's debate will be conducted in a looser town-hall format where questions are asked by the audience - a favourite setting for McCain and one he used in the party primaries this year and in 2000.
McCain and Obama will have two minutes to answer each question selected by Tom Brokaw of NBC news, the moderator, followed by a five-minute discussion between them.
New polls show Obama racing into a clear lead over his rival, with a one from CNN showing Obama with a 53 per cent lead compared to 45 per cent for McCain.
In New Hampshire, a key McCain target, Obama was up eight points in the CNN poll, while the race was tied at 49 per cent in solidly Republican North Carolina, where Obama stayed for debate preparation.