Harris spent the weekend cloistered in a historic hotel in downtown Pittsburgh where she focused on honing crisp two-minute answers, per the debate's rules.
Meanwhile, Trump has publicly dismissed the value of studying for the debate. The former president is chose instead to fill his days with campaign-related events.
"He can say outrageous things. It won't detract from his support. Harris, on the other hand, has the potential to drop, lose some enthusiasm, or she could gain it all, right?" said Wayne Steger, political science professor at DePaul University.
Steger said while Harris, a former prosecutor, is detail-oriented, she must keep policy issues simple.
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"If she can paint Donald Trump as not having new ideas and she's the future, then she creates that change candidate, and then, I think, is the frame she wants to go for," he said.
Trump is expected to improvise using the same predictable themes he used against President Joe Biden: immigration and inflation.
"I think that Kamala Harris will see a lot of this coming, and of course, her strengths as a former prosecutor are being prepared and having a game plan about how to respond when the expected and the unexpected happens," said Northwestern University Director of Debate Dan Fitzmier.
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Debate experts say Trump's strength is debate experience and his love for the camera, but the rules are different from past debates. There will be no opening statements, no studio audience, no pre-written notes or huddling with staff during commercial breaks, and microphones will be muted when it's not the candidate's turn to speak.
Since the last presidential debate resulted in a sitting president dropping out of the race, Tuesday's debate will be quite significant.
"Debates are consequential again, and for so many years, we kind of got used to them being a little boring. In this case, there's gonna be a huge audience," Fitzmier said.
The 90-minute debate will have two commercial breaks. As of now, the ABC debate is the only one scheduled between Harris and Trump. A vice-presidential debate is set for Oct. 1.
The Associated Press contributed to this report.