Donald Trump’s dominant performance in the Nevada caucuses takes the Republican Party one click closer to an outcome once thought unfathomable: that the flamboyant billionaire with no previous political experience and questionable conservative credentials really could become the GOP’s standard-bearer in November.

Mr. Trump won in Nevada with 46 percent of the vote, well ahead of Florida Sen. Marco Rubio (24 percent) and Texas Sen. Ted Cruz (21 percent).

Though only 5 percent of convention delegates have been allocated, that math will change quickly come March 1, Super Tuesday, with more than 10 states voting and one-quarter of GOP delegates at stake. Voters like to back a winner, and the more Trump wins – now three contests in a row – the more likely he is to win in the future.

“If one of the two senators wants to be the nominee, they have to put their squabbling aside and start focusing on taking down Trump,” says Republican strategist Ford O’Connell. “I expect to see a glimpse of that in Houston at the debate on Thursday.”

The question, then, is how they might do that. Some Republicans suggest that to beat Trump, you have to think like Trump: Attack him on his weaknesses.

And Trump has plenty, they say. Start with his thin skin, on display in the last Republican debate, when Jeb Bush went after him over eminent domain and for blaming his brother on the 9/11 attacks. The audience booed Trump, and he lashed out.

“Trump is kind of prickly and can be baited,” says Chip Felkel, a Greenville, S.C.-based Republican strategist who is not affiliated with a 2016 campaign.

The argument is that Trump is temperamentally unsuited to being president. New Jersey Gov. Christie tried that argument in the final debate before the New Hampshire primary. Perhaps the result speaks for itself: Trump won New Hampshire going away, and Governor Christie dropped out.

Other candidates have gone after Trump and flamed out. Texas Gov. Rick Perry attacked Trump early, going after this conservative credentials and calling him a “false prophet.” He was out of the race by last September.

Kentucky Sen. Rand Paul called Trump “a delusional narcissist and an orange-faced windbag,” in an appearance in January on Comedy Central’s “Nightly Show With Larry Wilmore." “A speck of dirt is way more qualified to be president,” Senator Paul added for good measure. Within days, he was out of the race, too.

Name-calling obviously accomplishes nothing, at least when it’s a Trump opponent on the attack. And it just validates Trump’s own colorful use of language when going after his adversaries. With Trump, aggressive language shows he’s a fighter – a quality that voters are looking for at a time of economic and international insecurity.

Perhaps the best way to take down Trump, some suggest, is to attack his perceived strengths – his success as a businessman and the notion that he’s a populist standing up for the little guy. His supporters don’t seem to care much about his four bankruptcies, or the fact that he inflates his net worth (he says $8.7 billion, Forbes says $4 billion), or that he has yet to release his tax returns.

But Trump could be vulnerable, observers say, over the thousands of employees who have lost their jobs over the years, as happened, for example, when Trump Plaza closed in Atlantic City in 2014. Then there’s Vera Coking, the widow whose Atlantic City home Trump wanted to tear down so he could build a parking lot for limousines, and the small businesses he tried to squeeze out of Bridgeport, Conn., so he could develop the land.

Finding those people and telling their stories is “roughly what the Democrats did to Mitt Romney, rendering him radioactive with many of the same working class voters currently backing Trump,” writes New York Times columnist Ross Douthat, referring to the Republicans’ 2012 nominee.

“Except with Trump the trick is subtly different,” Mr. Douthat continues. “Mitt was a numbers guy, so he was caricatured as a cruel Scrooge. But Trump is a salesman: That’s been a big part of his campaign’s success. And how do you flip a salesman’s brand? You persuade people that he’s a con artist, and they’re his marks.”

The story of the Atlantic City widow has already come up, briefly, in the campaign, both in one of the GOP debates and in an ad by Senator Cruz’s campaign, which he ran only briefly. In addition, the ad misstated the facts of the widow’s case – Trump did not succeed in buying her house – and that muddied the message. But the fact remains that Trump’s business history is fertile territory for arguments against him.

Important, too, is who does the attacking. And as the Republican nomination race winnows down to just a few candidates, it’s noteworthy that Senator Rubio – seen as the GOP establishment favorite to go one-on-one against Trump – has barely taken him on.

“Here’s my thing with Marco – I believe he’s competitive enough to do it, but I don’t know if he has the killer instinct,” says Mr. O’Connell.

Thursday’s debate, the last before Super Tuesday, could be the test.

Another avenue for taking down Trump is via the super-political action committees, the outside groups that independently support candidates. Some have taken on Trump, but with limited success. One called Make America Awesome claims it made headway with Iowa voters in an ad on eminent domain abuse.

"The Des Moines Register's final pre-caucus poll makes clear what Make America Awesome's data has shown for months: Trump-inclined voters will only be dissuaded from backing him if they see Trump as just another rich guy who's been screwing them over economically, rigging the system and then making bank while their lives get tougher," Liz Mair, who runs the super PAC, told the Washington Examiner.

Another super PAC, devoted solely to taking down Trump, released its game plan on Monday.

“Many have asked me, ‘What can be done to stop Trump?’" writes Katie Packer Gage, executive director of Our Principles PAC. “The answer is simple: TRY.”

Ms. Gage, who was deputy campaign manager for Mr. Romney in 2012, says that of the $215 million Republicans have spent in ads and voter contact so far this cycle, only $9 million – 4 percent – has been aimed at challenging Trump, while tens of millions have been spent attacking Rubio, Cruz, and the others.

Her favored argument against Trump: that he’s a “conservative of convenience,” who supports government-mandated health care, tax hikes, and Planned Parenthood.

The conservative Club for Growth has also announced a $1 million ad buy in two Super Tuesday states against Trump, though its previous ads seem to have had little effect.

To Trump, this is all just the Republican “establishment” trying to take him down and protect its turf.

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In the end, says Mr. Felkel, Trump may be the only one who can take down Trump: “I think his biggest weakness is himself.”

[Correction: This article was updated to correct the year Trump Plaza closed in Atlantic City.]