Between her 2000 Senate run and two presidential bids, Clinton has appeared on the debate stage nearly 40 times. Still, she has never prepared for an opponent quite as unpredictable as Trump.
In an email to supporters this week, Clinton touted her debate experience but acknowledged Monday's matchup is "the most important" yet.
More from NBC News:
Clinton Preparing for 'Different Trumps' at First Debate
Trump Supports Stop-and-Frisk Despite Policy's Condemnation
Trump Dismisses 'Narrative of Cops as a Racist Force'
This month, Clinton has hunkered down with top aides to study from the comfort of her own home. The bulk of Clinton's prep has been done in and around her house in Chappaqua, New York, partly due to her recent bout with pneumonia.
Following the disclosure of her illness, Clinton took three full days off the trail to recover and read up on briefing books.
And while the campaign is very tight-lipped on specifics, aides say they are preparing for the night to go in several directions.
The candidate herself has often said that she doesn't know "which Donald Trump will show up" to the first debate. Clinton's communications director, Jennifer Palmieri told reporters this week that the campaign is "preparing for the different Trumps that might show up."
At a Hamptons fundraiser last month, the former secretary of state asked the crowd for "thoughts or ideas" on her debate strategy against the Republican nominee. "Maybe he will try to be presidential and try to convey a gravity that he hasn't done before or maybe he will come in and try to insult and try to score some points," she speculated.
Recently, Clinton has vowed to "communicate as clearly and fearlessly" as possible "in the face of the insults and attacks and the bullying and bigotry that we've seen coming from my opponent."
Those familiar with her prep know she needs to be ready to take on any uncomfortable topics that Trump could possibly throw her way, a tactic Trump hasn't shied away from in the past.
Aides argue Clinton has a slight edge because she has so much experience debating one-on-one, whereas Trump spent most of the time in the primary season sharing the stage with many opponents.
The Democratic nominee opted for a fairly light schedule this week in order to practice for the debate. She only traveled to two battleground states — Pennsylvania and Florida — in order to accommodate enough prep time. She's taking full days off the trail Thursday and Friday, unlike her opponent, and has no public events scheduled over the weekend either.
One very guarded secret that has stayed under wraps, so far, is the question of who is playing Trump at these private sessions. Some have hinted that multiple people are taking on the role, in order to best prepare for the different tones Trump may strike.
Palmieri has called the debate stage a "great place" for voters to hear from Clinton in an "unfiltered" way.
The critical calculation will be: How much time can Clinton spend on the offensive debating against someone like Trump who will seek to put her on defense for most of the 90-minute discussion.
Every campaign tries lower expectations for their candidate ahead of a debate, and then pump up their performance afterwards, but Democrats are preparing for the spin wars to be especially important this year in shaping the public image of the debate.
One of Clinton allies' biggest concerns is that Trump will be judged against an unusually low bar, while Clinton will be judged against an impossibly high one. Aides have already started working the refs, urging reporters and pundits to hold Clinton and Trump to the same standard, and her campaign is sure to flood the airwaves with surrogates ready to declare Trump's performance a disaster and shame media figures whom, in their opinion, are too soft on Trump.
As the countdown clock to Monday night's first encounter ticks away, Clinton told radio host Steve Harvey Tuesday that she's ready for a heated encounter on the debate stage.
"I can take it," she said. "I can take that kind of stuff. I've been at this and I understand it's a contact sport."