These difficulty achievements will stack! You can start at this difficulty right away if you want, but it would likely cause you to play more hours in the game than needed. You can if you want, but instead, there is luckily a trick like in many other games where you only need to play the last level on the hardest setting.
Step 1: Beat game on easy
Step 2: Continue from menu. Select hardest difficulty.
Step 3: Exit back to menu after game starts. Load up Mission 8.
Step 4: Beat the last level
Hints for X-treme (Mission 8)
Do not use your powers, save it. It's best to have Wolverine's defense X-gene to give you one more health bar as well as health regen. You will need to level it up.
Groups of Enemies: You will want to use attacks and dodge when things get shot at you. Be careful, one or two hits can put you in a really bad situation. Focus on enemies that use projectiles.
Sentinel: This was the hardest part in my opinion. It's somewhat of a struggle up the building, but there's no real trick but to keep jumping and watching your timing. As far as the boss goes, it's best to have your power bar full if you can. If you have it, equip Quicksilver's X-gene set. When the sentinel's chest opens, press and start attacking. You may also choose to use Wolverine's set. This will let you heal quicker and do more damage, so you would want to wait for when you needed it. You will probably die a whole lot here, but you'll start to get used to the attacks. They are the same every time you play. When the sentinel puts the energy bombs on the ground, you can still attack his chest on the side when he puts one in front of him. You will very much want Wolverine's defensive gene for this fight!
Tip: People have found you can hit the sentinel's arm when he tries to hit you to help with the fight.
Bastion: Not as tough as a fight once you get the hang of the attack patterns. If you have Quicksilver's Utility gene and have maxed out all levels, you will be in extremely good shape! It will allow you to make short work of the teleporting. If not, most other utilities will work for speed. Once you get him to his 3rd time for repairing shield, you'll hopefully have 4 bars of power. Activate your ultra power and finish him off.