Tuesday, he'll be playing clean up for Donald Trump, the most unpredictable and unruly candidate to ever top the Republican ticket.
Since the first presidential debate last week, Trump has become consumed by controversy marked by his own stumbles, late-night tweets and capped by The New York Times report that he lost over $900 million in 1995, which may have helped him avoid paying federal income taxes for 18 years. Trump added to his troubles Monday when he said that veterans commit suicide because they "can't handle" the stress of war.
Trump has defended his tax filings by saying he knows the tax code well and can use that knowledge to better fix it.
"I have legally used the tax laws to my benefit ... Honestly, I have brilliantly used those laws," Trump said Monday in Pueblo, Colorado
Tuesday's vice presidential debate in rural Virginia will be the biggest political moment for Pence and Clinton's running mate, Virginia Sen. Tim Kaine. Their job: defending the top of the ticket from attacks while also getting in some hits of their own.
Pence previewed some of his material Monday, during a pre-debate rally in Ashland, Virginia.
"Hillary's record on foreign affairs alone could literally take up the entire 90 minutes and it wouldn't be pretty," Pence told the crowd.
He also hinted at the tough balancing act of trying to play up his credentials, but not cutting into the job of defending Trump and attacking Clinton, saying "I hope we get to talk about our records as well."
Pence has already spent much of his almost three months running with Trump explaining and smoothing over the businessman's roughest edges and toughest self-inflicted wounds. (It's what has led at least one Indiana Democrat to dub Pence "the chief pooper-scooper.")
A Pence spokesman said he did not want to get into hypothetical questions about Pence defending Trump's record, but pointed to their joint appearance together on "60 Minutes" when Trump said he did not expect Pence to use the same language as him.
Pence has withstood some tough grillings over Trump's positions without giving any ground already.
In late August, as Trump's advisers attempted to explain that he would stake out nuanced territory on immigration, Pence argued extensively with CNN's Jake Tapper that Trump would not be changing his positions at all.
"Nobody was talking about illegal immigration when Donald Trump entered this campaign. He was attacked from day one for putting the whole issue of the violence that is derived from certain individuals that come into this country illegally on the table," Pence said on CNN's "State of the Union.
Pence has been preparing weekly for the debate since he was picked by Trump, aides say, and Wisconsin Gov. Scott Walker has been playing the role of Kaine.
But Tuesday's dynamics promise to be immensely tougher than his 2012 debates in Indiana. Back then, Pence was the front-runner for Indiana governor, carrying the mantle of the popular outgoing Gov. Daniels and running almost like an incumbent.
Through three debates, Pence was poised and almost flawless in his ability to duck questions and stick to a carefully scripted message of taking Daniels' conservative management of the state "from good to great."
Pence split the stage with a former Indiana state lawmaker, John Gregg, known for his trademark walrus mustache and Rupert Boneham, a former reality TV star running on the Libertarian ticket.
Pence's message discipline is legendary, if a bit rigid, and has only clearly gotten him in trouble once, during a scathing interview
with George Stephanopoulos last year in the middle of Indiana's "religious freedom" battle.
Pence's public approval in Indiana tanked after last year's handling of the "religious freedom" push and other stumbles, including an attempt to start a state-run news service. And he was locked in a surprisingly tight re-election bid with Gregg earlier this year when Trump picked him as his running mate, in large part for his ability to stick close to a script.
By the start of last month, a local poll by WTHR and Howey Politics
found Hoosiers were evenly split between seeing Pence in a favorable and unfavorable light since joining Trump.
"I think Hoosier voters are looking at Gov. Pence and they see him in a new light, they see him in a different context, they see him in a national context and he's popular because of it," Indiana Republican operative Mike O'Brien said last month on the long-running Indiana political show, "Indiana Week in Review."
But Ann DeLaney, a longtime Democrat, fired back: "I think they see him in a new light -- he's the chief pooper-scooper."
"I mean all he's doing is running behind trying to say, 'He really didn't mean what he said,'" she said. "If he was going to lose for governor, I guess it makes more sense to lose for vice president."