First, win re-election this year, and by 10+% (tough, but not impossible now I must concede) bc right now his only actual victories are a small 0.4.% victory in the GE and a massive primary win due to trump’s heavy hand of influence;
Second, as said above, hope trump doesn’t run
Third, if he gets the nomination, pick a sane VP choice like Tim Scott, which could prove crucial in places like Georgia, which the gop has to win back to have a plausible path to 270 (WI/PA alone won’t be enough).
Fourth (and this is out of his control as a challenger), is the national environment. Whether it’s Biden or not, the incumbent party must retain a 50% disapproval or higher in the aggregate. And even then, no matter how bad the Dem approvals are, no Republican is going to get above 320 in the electoral college (2016+NV/NH). It’s just not happening due to polarization.
This would definitely be a gamble, as it almost always in electoral politics. Often it's just timing that decides who becomes president, governor or senator. If you run in the wrong year, you're not getting there. Some high profile Democrats decided it was better to sit out the 1992 election as it looked like Poppy Bush's reelection was a shoe-in in 1991 and the aftermath of the first Gulf War.
If DeSantis doesn't run in 2024, he might not get a better chance even later on, regardless of his age. After his term expires in 2027, he at least needs something else to stay relevant and not be old news beyond the 2028 cycle. He actually would depend in Biden winning reelection to have a strong opening in 2028. If Biden loses or retires and Kamala loses to general election to another Republican, DeSantis obviously can't challenge the Republican president for the nomination and would have to wait for 2032. And even if he manages to stay relevant enough until then, he either runs to succeed a two term Republican in an election that would favor the Democrats. Or, if Biden's Republican successor is a one termer, DeSantis would face an incumbent Democratic president and possibly be an underdog here. Lastly, if a term-limited Trump is the incumbent in 2028, the Democratic candidate might very well be favored after another chaotic four years and no incumbency advantage with the Republicans. So either way, it's a gamble. I'd at least try in 2024 in his position. Even if he loses to Biden, he could still try again four years later unless he got completely wiped out.
