Not if there was an "al Qaeda" attack on the state of the union address like one of the Clancy novels and the president, VP, and speaker of the house were killed. (If the speaker made it through the attack, he/she could be heart attacked due to the trauma.)
Next up is President pro Temp of the Senate (which she could easily get if they got a majority) and next is SecState.
And she wouldn't even have to endure a campaign or get enough votes.