But the two other candidates onstage, the entrepreneur Vivek Ramaswamy and former Gov. Chris Christie of New Jersey, will do all they can to grab the spotlight in the hope of revitalizing their flagging campaigns.

Here’s what to watch:

Who will stand out on a less crowded stage?

The “will he or won’t he” speculation about whether Mr. Trump would participate in the previous debates in Wisconsin, California and Florida is gone ahead of the gathering in Alabama. The former president’s decision to sit out the events has not hurt his standing in the polls, and the question for many now is whether he would show up to a debate in the general election next fall.

But as the field narrows by attrition, the final four will have more time to make an impression on Republican primary voters who have yet to decide.

Gov. Doug Burgum of North Dakota on Monday became the latest candidate to drop from the race, although he had failed to make the stage for the last debate. The withdrawal of Senator Tim Scott of South Carolina will be felt more acutely, since he probably would have qualified for Wednesday’s event. His debate performances were largely unremarkable but he made a small splash in Miami last month when he showed up with his girlfriend.

The most memorable lines of the last two debates involved Ms. Haley skewering Mr. Ramaswamy. In September, she told her younger rival, “Every time I hear you, I feel a little bit dumber,” and last month she called him “just scum.”

Those lines raise an important question for Mr. DeSantis as he tries to fend off Ms. Haley’s rise in the polls: Can he take her on more directly and win?

Mr. Ramaswamy appears likely to continue his strategy of denigrating and baiting all of his opponents except for Mr. Trump, though the efficacy of his insult-driven blitzkrieg seems to have diminished since he shocked the field in Milwaukee in August. In Iowa City on Saturday, he said he had been “brutally frank in the last debate,” adding, “I don’t intend to stop doing that now.”

Mr. Christie faces a loftier question: Is his stated goal of thwarting another Trump presidency better served by dropping out and letting a rival consolidate the anti-Trump vote?

Can Haley keep her winning streak alive?

The former South Carolina governor has parlayed her debate performances into a real sense of momentum. Yes, she remains far behind Mr. Trump, the man who made her his first United Nations ambassador, in national polling, but her trajectory is on a slow, steady climb, unlike those of her onstage rivals.

Wednesday’s debate is the first since the political network founded by the billionaire conservatives Charles and David Koch endorsed Ms. Haley, promising to mobilize an army of grass-roots door knockers behind her. It is also the first since Jamie Dimon, the chief executive of JPMorgan Chase, began encouraging other major donors and Democrats to back her as the last hope of thwarting Mr. Trump’s nomination.

She needs to reassure those new backers that they made a solid bet. To do that, she will have to find the zingers she used to dismantle Mr. Ramaswamy, and turn them on the candidate now in her sights, Mr. DeSantis.

She still needs to figure out, however, whether she is the candidate for those inside her party and out who fear and loathe Mr. Trump, or whether she wants to appeal to Trump supporters as a fresh face to pick up his mantle. If she is the former, she may only get so far in a G.O.P. that still broadly approves of the former president. Appealing to Trump likers and loathers has been the trick that no Republican has solved.

Can DeSantis wrest the mic from Ramaswamy?

After taking glancing shots at Mr. Trump for months, Mr. DeSantis laid into him at length on Tuesday.

He castigated Mr. Trump for bragging about the endorsement of a Black Lives Matter activist, for criticizing Mr. DeSantis’s strongly anti-abortion record, and for somehow blaming the Florida governor for the College Football Playoff selection committee’s snub of Florida State University, which was not selected to vie for the championship despite an undefeated season. (The University of Alabama, in Tuscaloosa, was the beneficiary of that snub, so watch for college football talk on Wednesday night.)

But Mr. DeSantis’s main criticism was of Mr. Trump’s refusal to debate: “I don’t think he can stand there for two hours against me and come out on top,” he said. “I think they know that, and I think that’s why they’re not doing it.”

Clashing with Mr. Trump is vital; after all, you can’t win the nomination without beating the front-runner. But Mr. DeSantis has to blunt Ms. Haley’s rise as well.

In Tuscaloosa, Mr. DeSantis needs to take the microphone away from Mr. Ramaswamy, who has faded to fourth place in national polling averages. Ms. Haley, by contrast, is now solidly in second place in New Hampshire, neck and neck with Mr. DeSantis in Iowa and threatening him nationally.

Mr. DeSantis’s pressing task is to reassert his status as the Trump alternative, and for him to do that, the debate cannot devolve again into a cage match between Ms. Haley and Mr. Ramaswamy.

What is Chris Christie’s endgame?

For reasons of ego, unrelenting self-confidence or designs on his future, Mr. Ramaswamy, a political neophyte with nary an elected office to his name, is probably not leaving the primary race anytime soon. The money he is spending from his own bank accounts — $17 million as of Sept. 30 — can keep his campaign afloat as long as he wishes.

Mr. Christie is, in many respects, Mr. Ramaswamy’s opposite, a career public servant without a vast fortune to tap, whose campaign’s raison d’être is to diminish Mr. Trump’s stature, not to lionize him as the 21st century’s greatest president. But the former New Jersey governor finds himself at a crossroads in Tuscaloosa.

He barely made the debate stage, just qualifying under the Republican National Committee’s tightening requirements — polling at 6 percent or higher in national or early-state polling, and garnering 80,000 unique donors.

And his third-place status in New Hampshire, with around 12 percent of the vote, could be seen either as a strength or as a spoiler for the aspirations of the candidate in second place, Ms. Haley, who needs a strong showing in the Granite State to slingshot her into the primary contest in her home state, South Carolina.

Mr. Christie continues to denounce Mr. Trump’s fitness for office in ways his Republican rivals won’t, challenging the former president as a would-be dictator threatening to end democracy as we know it. But that line of attack has proved ineffective among Republican primary voters.

Megyn Kelly is back. How will she handle the absent Trump?

The 2016 presidential campaign might seem like ancient history, but for many Americans, Mr. Trump’s treatment of Megyn Kelly, then a Fox News anchor, during the debates secured his reputation as a misogynist.

After Ms. Kelly questioned him forcefully in one debate, he came back with, “You could see there was blood coming out of her eyes, blood coming out of her wherever.” Ms. Kelly was defiant in the face of angry Trump supporters, declaring that she would “not apologize for doing good journalism.”

Wednesday’s debate, which will be carried by a cable news newcomer, NewsNation, will have a considerably smaller audience than those Fox showdowns in 2015 and no Mr. Trump — but Ms. Kelly, who now hosts “The Megyn Kelly Show” on Sirius XM, will be back.

No doubt, she will be tough on the four participants. The question is, how hard will she press them to take on Mr. Trump?

Ms. Kelly will be sharing the moderators’ desk with Elizabeth Vargas of NewsNation and Eliana Johnson of the Washington Free Beacon, an all-female panel tilted to the right. The debate will be televised on the CW starting at 8 p.m. Eastern time, and streamed on the NewsNation website and the conservative social media site Rumble.

Anjali Huynh and Maggie Astor contributed reporting.