Djokovic insists there will be no letdown physically or emotionally after reaching the final in Paris for a sixth time with an epic triumph over 13-time champion Nadal.
World number four Medvedev had a shot at breaking that stranglehold in the US Open final in 2019 against Nadal but went down in five sets.
"I wouldn't be surprised to see Daniil win the tournament," Tsitsipas, ranked sixth in the world, told reporters after his 6-4 6-2 7-5 defeat to Medvedev in the semi-finals.
The relentless Russian will contest his first final at Melbourne Park on Sunday and look to claim his maiden Grand Slam title after beating Tsitsipas 6-4 6-2 7-5 at a floodlit Rod Laver Arena.
Yet Medvedev has now won 20 successive matches and 12 against top-10 opponents, including beating Djokovic on the way to winning the ATP Finals.
The 34-year-old was playing his first tournament of the year after back tightness, following a stint in Australian quarantine, kept him out of the ATP Cup team competition.
The pair were born within weeks of each other and were often pitted together as juniors, but Greek fifth seed Tsitsipas swatted the Swede 6-4, 6-1, 6-1 on John Cain Arena.
Nadal is looking to edge ahead of Roger Federer who also has 20 Slam titles to his name, with the injured Swiss not playing in Melbourne. He plans to return to the ATP Tour at Doha next month.