When I target an opponent's ship and use Cluster Missiles, I can attack twice. Does my opponent defend twice as well? If I use Gunner or Luke, then I assume my opponent rolls to defend a third time, as well?

If you look at the rules reference under the Attack heading you'll see a sequence of steps you need to follow to perform an attack - that includes your opponent rolling defense dice.

So anything in the game that is described as an attack must follow those steps*

That's why any game effect that just instructs you to roll an attack dice and / or suffer damage is not an Attack - it's just damage or potential damage.

* Cluster Missiles and Twin Laser Turrets break this rule ever so slightly as although the card instructs you to perform the attack twice, you skip step 1 ( declare target) for the second attack

Each time you make an attack you roll the attack dice and the defender rolls his defence dice (if he has any). Extra attacks do not mean they're a free attack that he can't defend against.

Cards that have multiple attacks, like Cluster Missiles and Twin Laser Turret follow all the steps for a normal attack, except the Declare Target step. You only do that once. So when using CM or TLT, both attacks must be on the same target.

If you have a Gunner or Luke (crew), that is a separate attack and does have it's own Declare Target step, so you can target a different ship to what you previously fire on (and missed).

Each attack is a separate event that is defended independently of any previous attacks.

This means that a new defense is rolled and that defense would NOT benefit from any Focus or Evade tokens spent on the previous defense.

When you use Cluster Missile or TLT and a Gunner effect you need to consider timing. The first attack with a Cluster or TLT can trigger Gunner allowing you to make a primary weapon attack; however if that attack is taken you are NOT allowed to make any additional attacks meaning the second attack from those weapons never happens. If the first attack does not use Gunner (it hits or it isn't used) then the second attack still happens and if it misses then the Gunner effect can trigger allowing for a third attack.

Thank you all.