"Am I missing a 'box'?"

What about the entire financial picture?

"Also, if he needs to set aside 10k, does that all go aggregate to the IRS, and at the end of the year, that is divided amongst income tax, self-employment taxes, Medicare, etc?"

It's just Fed Tax Prepayment. It isn't divided or allocated.

If you have a W2 job and decide to use 0 withholding, you would pay Estimates if your financial picture requires it. If you have a W2 person and a Sched C person, the W2 person can increase their withholding to cover the family likely Fed Tax liability.

It's just a prepayment process against the entire 1040. Not using anything except the Sched C is not the full picture.