The dynamic has left his opponents preparing for an unusual scenario: debating among themselves while the front-runner with a commanding lead is entirely absent.

Still, for Mr. Trump’s rivals, the debate provides the biggest audience of the race to date, and their first chance to not only make an impression but to make the race a true contest.

Senator Mitt Romney, a Republican who ran the presidential debate gantlet twice and is his party’s most prominent elected Trump antagonist, offered this advice: “The key for them is not to focus on each other but the person who’s at the top. You gotta punch up.”

Yet even the most viral moment could quickly be swept away in a wave of Trump-driven news. “In 99 out of 100 futures,” said Newt Gingrich, the former Republican presidential candidate and House speaker, “Donald Trump is the Republican nominee and he doesn’t even breathe heavy.”

But the eight candidates have a shot to present Republican voters with an alternative. How they make their case could make the 2024 primary a contest and not a coronation.

Here are nine things that are likely to define the debate.

How present is Trump, even when he’s absent?

A significant portion of the debate will most likely revolve around Mr. Trump, his criminal indictments, his continued questioning of the 2020 election and his responsibility for the Jan. 6 attack on the Capitol. While the candidates have been asked about those issues frequently, a debate allows for follow-up questions — heightening the possibility of a misstep.

Mr. Trump will still put his mark on the moment. He has announced plans to try to upstage the debate with the release of a recorded online interview with the former Fox News host Tucker Carlson.

And on Thursday, the former president plans to surrender to the authorities in Atlanta to face charges in the case accusing him of election interference, an appearance likely to dominate the news cycle and cut into any bounce his rivals hope to receive from the debate.

Perhaps the candidate with the most at stake on Wednesday is Gov. Ron DeSantis of Florida. The DeSantis team expects him to be the target of attacks. “The other candidates, a lot of them don’t really say much about Trump, and they focus more on me,” Mr. DeSantis said on Fox News Radio last week.

Mr. DeSantis is viewed as Mr. Trump’s strongest challenger, but he has faced weeks of bad press, campaign shake-ups and sinking poll numbers — in what can be a self-reinforcing downward cycle. The debate is his opportunity to change the narrative.

But that strategy was complicated last week when a series of documents and a debate strategy memo were published on the website of a firm associated with the super PAC that has taken over some of the basic elements of Mr. DeSantis’s presidential campaign.

The strategy memo outlined “four basic must-dos” for the governor to parry away the attacks, including going after Vivek Ramaswamy, the entrepreneur and author who has gained ground in recent weeks, and defending Mr. Trump in the face of attacks from Chris Christie, who has seized the role of chief Trump antagonist in the race.

The release puts Mr. DeSantis in a bind. If he punts on those attacks, he could miss the opportunity to undercut key rivals. If he follows through, he may look inauthentic or even like a puppet.

Can Pence make Republicans reconsider?

In mock debate sessions, Mike Pence, Mr. Trump’s vice president for four years, has prepared to contrast his staunch opposition to abortion, support for Ukraine and his focus on economic growth with the other candidates on the stage. Yet there’s one issue that some of his advisers believe he must address to pull out of single digits in polling: his role certifying the 2020 election. The issue has dogged Mr. Pence, who has been criticized by Mr. Trump’s supporters and labeled a traitor.

The debate, his team hopes, will still give Mr. Pence a bigger stage to make the case that he often does on the trail — that he was just following his constitutional duty on Jan. 6.

Mr. Ramaswamy, a wealthy entrepreneur and political novice, has gained traction by wooing MAGA supporters who want a next-generation version of Mr. Trump. He has taken a series of hard-right positions and has said Mr. Trump’s “America First” agenda does not go far enough.

Mr. Ramaswamy has taken a more informal approach to preparing for the debate, holding conversations on policy with advisers as he travels the country aggressively, visiting nine states in the last week. A 38-year-old Harvard graduate, Mr. Ramaswamy has focused on studying foreign policy in particular. Victoria Coates, a former Trump administration official, has been among those giving him briefings, according to a campaign adviser. He prefers less structured sessions that don’t feel overly produced, the adviser said.

Many far more politically experienced contenders have met their end under the bright lights of the debate stage. Can Mr. Ramaswamy’s performance match his bluster?

How do policy differences shape the debate?

Two issues have divided the Republican field more than any others: abortion rights and support for Ukraine in its war against Russia. The Ukraine war has exposed a rift between the foreign policy hawks and the anti-interventionist wing of the party.

On abortion rights, an issue that has powered Democratic victories since Roe v. Wade was overturned last year, Republicans have struggled to unify around a central position. Senator Tim Scott of South Carolina says he will fight for a 15-week federal ban, Mr. Pence has expressed support for a six-week ban and Mr. Christie says the issue should be left to each individual state.

Mr. Pence, Mr. Scott and Nikki Haley, the former United Nations ambassador under Mr. Trump, plan to highlight these differences, seeing an opportunity to win support among different party factions. How Republican voters respond will offer some early clues into the ideological future of the party, particularly in a post-Trump era.

Will Christie turn his firepower on DeSantis?

Aside from Mr. Donald Trump, Mr. Christie is the most experienced debater in the field, with a knack for landing memorable attacks. He participated in eight face-offs during the 2016 election, and helped coach Mr. Trump for his presidential debates in 2020.

So far, he has focused much of his firepower on Mr. Trump — in a candidacy that some rivals see largely as a kamikaze mission to prevent the former president from recapturing the nomination. The debate offers Mr. Christie an opportunity to take aim at those aligned with Trumpism, even if they are opposed to Mr. Trump. In recent days, he has signaled that such attacks could be coming, particularly against Mr. DeSantis and his claims that he is the most electable in the field.

“If you like Coca-Cola and Coke comes out with New Coke, and Coke is still available, well, you’re going to buy Coke because what do you need New Coke for?” he said in a recent town hall in New Hampshire, arguing that Republicans needed a truer alternative to Mr. Trump than Mr. DeSantis. “Ron DeSantis is New Coke.”

The senator from South Carolina has campaigned across the country with an upbeat, future-focused message that leans heavily on his compelling personal story. There has been some evidence it’s working: In recent weeks, his standing has crept up steadily in polls.

But while Mr. Scott has been gaining ground, he remains mired in single digits in most early-state polling. The debate is a chance for him to get a bounce. But will a positive message break through in a debate that could easily become a referendum on Mr. Trump and the past election?

Can Haley make it happen?

Ms. Haley, a former South Carolina governor and U.N. ambassador, entered the race in February, before any other candidate aside from Mr. Trump. She has campaigned at a grueling pace through Iowa and New Hampshire. But so far, she has little to show for her efforts. Her poll numbers have barely moved. And Mr. Scott, her home state rival, has surpassed her in both early-voting states.

Ms. Haley has urged voters not to count her out in not-so-subtle ways, showing up at the Iowa State Fair in a shirt that read, “Underestimate me. That’ll be fun.” Yet primary voters have expressed little interest in the lone woman in the Republican race.

Aides say she views the debate as the kickoff to the fall season of the campaign, when voters will start tuning into the primary race. But can she can make them pay attention?

How will lower-tier candidates introduce themselves?

Gov. Doug Burgum of North Dakota went to great lengths to qualify for the debate stage, at one point even offering $20 gift cards in exchange for $1 donations. But so far, the billionaire former software executive has yet to break 3 percent in Iowa. The issue, Mr. Burgum and his team argue, is largely one of familiarity. The debate offers Mr. Burgum his biggest — and possibly only — chance to make his pitch. “The important part was making the debate,” he said in a brief interview in Iowa.

Former Gov. Asa Hutchinson of Arkansas faces a similar need to introduce himself to voters. He said the best advice he received for the big night was blunt: “Don’t make it boring.”

For his part, Mr. Burgum is not placing a lot of pressure on his performance on Wednesday night. “For us, we don’t have to hit home runs, grand slams, any of that stuff,” he said. “We’re just on the stage with everybody else, being ourselves.”