With poised to win the Republican nomination, Democrats are already gathering ammunition to use against him in the general election.
In more than a few instances, the best fodder has been provided by the candidate himself.
A case in point: As the economy was rising late last year as a major issue for voters, McCain in New Hampshire delivered this grenade, with its pin still in it: "The issue of economics is not something I've understood as well as I should," he said. "I've got Greenspan's book."
Those are not the only words that will come back to haunt him in November.
From the economy to Iraq to immigration to abortion, the Arizona senator's lengthy voting record and his primary season offerings to the Republican Party's conservative wing provide a deep vein for opposition researchers to mine for shifting positions and policy inconsistencies.
Democratic National Committee Chairman Howard Dean is already moving to redefine the presumed Republican nominee. In a fundraising appeal sent out Wednesday, Dean called McCain "a media darling" and warned that "from Iraq to health care, Social Security to special interest tax cuts to ethics, he's promising nothing more than a third Bush term."
The tough part for Democrats will be making any criticism stick. Republican rival Mitt Romney tried to no avail. The sharp, eleventh-hour assault launched by conservative talk show host Rush Limbaugh and a cadre of high-profile conservatives also failed to derail his candidacy.
Doug Schoen, a former adviser to President Clinton, says the Democrats must act quickly. "The trick is to get him on the flip-flops and not let him get back to the center where he can be a real force," he said.
The appeal of a flip-flop assault is that it could undermine McCain's reputation for taking tough stands and sticking with them no matter how the political wind blows.
Carter Eskew, a former adviser to Vice President Al Gore, puts it this way: "Go right after his strengths. Take the Straight Talk Express and push it off the rails."
Democrats are also convinced McCain is standing on soft ground on policy issues that are foremost in voters' minds. Tad Devine, a strategist to 2004 Democratic nominee John Kerry, says those substantive critiques should be the first line attack.
On the economy, McCain has tried to distance himself from his self-deprecating comment about his understanding (or lack thereof) of the economy. But his attempts have fallen flat in part because he's made the mistake of alluding to the weakness more than once.
In 2005, he sat down with Stephen Moore of the Wall Street Journal, and said: "I'm going to be honest; I know a lot less about economics than I do about military and foreign policy issues. I still need to be educated."
On the campaign trail, he's also suggested he'd look for a vice presidential running mate with strong economic credentials to balance weaknesses of his own. He tried to take that one back, too.
Those comments, coupled with McCain's relatively thin economic message, could leave him vulnerable to recasting by the opposition.
One broad theme that will be used against him is that he's offering little more than an extension of the Bush economic policies that have exacerbated the nation's wealth gap and brought about a return of giant deficits.
Democrats could also take some sharper shots at his economic plan, which centers on two core messages: cutting taxes and cutting spending.
On taxes, McCain's votes against President Bush's 2003 tax cuts and his explanation for them are likely to become major talking points. "I just thought it was too tilted to the wealthy and I still do," he said of those tax cuts. "I want to cut the taxes on the middle class."
Democrats are sure to argue that if the Bush tax cuts were "too tilted" toward the rich in 2003, they are only more so now.
McCain will have to square his previous comments with his call today to make Bush's tax cuts permanent and add new cuts for the middle class.
To recover the lost revenue from the tax cuts, McCain is promising to cut earmarks and wasteful spending -- a line that plays well with his party's fiscal conservative wing.
On this point, the senator is on firmer footing since he's earned solid credentials on the issue by leading some major fights against pork barrel projects.
And McCain himself isn't exactly simon-pure on the issue. He has secured special funding for Arizona projects, including a $10 million allocation he sought for the University of Arizona to build a center honoring the late Supreme Court Chief Justice William Rehnquist.
McCain's unyielding support for the military surge in Iraq could be another troublesome area. While many Republican primary voters viewed his steadfastness as a sign of strength and leadership, his position will be more precarious when courting a general election audience.
According to a January Los Angeles Times/Bloomberg poll, 20 percent of registered voters want to withdraw immediately; 43 percent want American troops home within a year. Only 31 percent of registered voters - mostly Republicans -- said the troops should stay as long as it takes to finish the job in Iraq.
McCain was already facing those headwinds before he said in January that he "would be fine" with having American troops stationed in Iraq for 100 years, provided they were not being harmed or killed.
Democrats will leap on that remark to try to paint him as a warmonger, hopelessly out of touch with the American electorate and blind to their version of realities in Iraq.
They are also likely to push back against McCain's penchant for blaming the Iraq campaign's problems on former Defense Secretary Donald Rumsfeld.
That rhetoric allowed McCain to criticize the pace of progress in Iraq without directly targeting Bush during the primary season. But Democrats will try to link McCain with Bush.
"The Iraq war wasn't just a bad strategy implemented by a bad secretary of defense. It was the wrong strategy for the president and McCain was in the middle of all of it," said Devine.
McCain's decision to highlight - and enhance - his conservative credentials for the primary race has created new general election vulnerabilities he didn't have during his 2000 presidential run.
The most potent argument the Democrats will make: That the McCain of 2008 is a paper-mache version of the Maverick McCain of 2000.
In 2000, many independent voters -- and even some Democrats - admired McCain when he took on the Rev. Jerry Falwell and conservative Christian broadcaster Pat Robertson by calling them "agents of intolerance" within the party.
This year, he courted both Falwell and Robertson in an effort to win over evangelical voters.
In 1999, McCain said he didn't want to see Roe v. Wade overturned because it could force "women in America to [undergo] illegal and dangerous operations."
Today, McCain says repeal of the landmark abortion rights Supreme Court decision "wouldn't bother me any."
On the volatile immigration issue, McCain saw his fundraising dry to a trickle last summer after he led the charge for Bush's comprehensive reform legislation.
Today, McCain has recalibrated his stance, saying he would push for strengthening the border to block illegal immigration before dealing with those already here.
McCain also has remained relatively silent on whether that means he would take up the Bush comprehensive bill anew after securing the borders - a question the Democrats will try to force him to answer.
Then there are the matters of McCain's advanced age and his temperament.
If he wins the general election, he will be 72 years old when he takes the oath of office, the oldest of any president. He's also had three bouts with melanoma, a skin cancer.
On the campaign trail, he's joked about his age and, at one point, casually suggested he might serve only one term. He's also said he's learned to control his temper.
Democratic strategists tend to discount either issue as a major line of attack on his candidacy, barring the sort of You Tube, "macacca" moment captured on film that derailed former Virginia Sen. George Allen's re-election campaign and presidential aspirations.
But that's not to say his opponents might not give it a shot.this week on CNN seemed to be testing a line for a McCain match-up.
McCain should be honored for his "half a century of service to this country," the 46-year-old Illinois senator said, but he's "not the person who is going to lead this country in a new direction."
Kenneth P. Vogel contributed to this report.