Not knowing what you don't know is the biggest challenge!
As much as one studies, prepares, and talks to mentors every dream starts off as being a "wild ride" full of disappointments and surprises. It's as if life tests you to see if you "really want" to make it happen. However waiting for the "perfect time" can hold one back. At some point one has to just "jump" and hope to sprout wings or catch a good wind while learning along the way.
Just about every mega success story contains moments where the business was on the brink of going under or facing major challenges.
There was a choice to fold up the tent or persist until they got a "yes". Also knowing when to sell the business can be beneficial.
No one knows ahead of time what their biggest challenge is going to be. It could be finding customers, meeting demand, running out of cash, too much inventory, a major shift in trends and being unwilling or unable to adapt.
I'm sure "Blockbuster Video" and "The Sony Walkman" never saw "Netflix" and "Apple's iPod" coming.