Learn Italian: Lui non può guidare, è stanco. - He cannot drive, he is tired.

Because it comes right after the modal verb può (can/is able to). In Italian, when you use a modal verb like potere (to be able to) or dovere (to have to), the main action verb that follows it stays in the infinitive (the dictionary form ending in -are, -ere, or -ire).

Where does the word non (not) go when using a modal verb?

non always goes immediately before the conjugated verb. In this sentence, it goes right before può to make non può guidare (cannot drive).

Why doesn't the second part of the sentence say lui è stanco?

In Italian, subject pronouns like lui (he) are usually left out because the verb already tells us who is doing the action. The sentence includes Lui at the very beginning for clarity or emphasis, but it isn't needed again before è stanco.

If we were talking about a woman instead, how would this sentence change?

It would become: Lei non può guidare, è stanca. The pronoun changes to Lei (she), and the adjective changes its ending to -a (stanca) to match the feminine gender.