Successfully complete campaign mode on the hard difficulty setting to unlock Gray Alien in multi-player mode.
Find and scan all five databank items in a level to unlock the secret for that level. The final secret of the game is unlocked when all prior secrets have been found.
Successfully complete campaign mode on the medium difficulty setting to unlock the hard difficulty setting.
In the earlier stages of the game, there are a few cabinets of the original Area 51 arcade game, complete with red and blue light-guns. If you melee attack the arcade machines you will usually get a life syringe.
Soon after meeting Dr. Cray, you will reach an infirmary where you will find clones of Mr. White walking around, mumbling, and rambling on. On the back of their lab coats you will find a Masonic lodge (a symbol of the Free Masons) suggesting a connection between the Masons and Illuminati.
During the training levels, scan everyone that you can. You will find some interesting equipment of the MPs, including adult diapers and condoms. Additionally, hold Right Analog-stick Down (with the default controller configuration, or in the opposite direction in the inverted configuration) until your scanner stops moving and you appear to be looking at your feet. You can now scan yourself and see information about Cole.
When you reach "Lies of the Past: Checkpoint 4", you will ascend in an elevator. Exiting the elevator, you will see a replica of the Moon's surface, a model of the U.S. space suit, and a shuttle the United States used to reach the Moon. This is in reference to the Moon Landing Conspiracy, claiming that the U.S. never actually reached the Moon, and faked the landing to beat the Russians in the space race. Additionally, go to a building behind the crane operations and scan a top secret file. Go back to the secrets in the campaign menu and play Doctor Cray's diary to hear him say something similar to "Man certainly has been to the moon but the horrors of the alien life form that reside there have never been reviled to the public." This refers to the theory that there is alien life form on the moon and that the government chose to hide it from the public.
Search the dead soldier in one of the elevators where Cole starts the level to find a small key. Use it to open the small lockers in the first power conduit pit to find a databank item. It will upgrade the alien grenade so that it will track targets.
Go into the fourth room in the level, where you can see the monorail you entered the level from out of the window. Push the computer console there and it will say "Lifter activated". Make your way back outside to the monorail. You can now stand on it. Run all the way to the back of it and you will be warped to a strange room with sharks that have machine guns attached to their heads.
To defeat Grays that use shields, mutate and fire parasites at them. It will bring down the shields faster than any other weapon in the game.
When fighting the Super Beast, rather than running straight at him, run around in a circle. When he gets near an explosive barrel, shoot it. It does more damage then the BBG. Watch out for his plasma shooting arm as well. When you finish, Edgar will talk to you, and you get to see him.
To defeat the Super Theta, you will use generally the same strategy as defeating the Theta except for a few things. It is recommended that you leave at least one shot in your Meson Cannon for him because of how much damage the weapon will do. Do not worry too much if you miss, because the Super Theta is still very easy. After you shoot him with the cannon, transform into mutant form and attack him with melee if your health is full or with the parasites if it is not. After a few hits it will leap up onto one of the four cryo-chambers and break it open, releasing the alien amoebas. These things must be meleed because the parasites will not trace them. Wasting the contagion on them will only drain your energy. They are not too difficult to hit in mutant form, because the "mutant vision" slows them down. Also, do not stand underneath the chamber that the Super Theta is breaking open, because afterwards it will drop almost directly underneath and will deal either fatal or nearly fatal damage when it hits the ground if you are there. However, after it does land, move in close and melee it for a few hits. The amoebas will not drop down immediately. After you kill the amoebas, start shooting parasites and using melee against the monster. When it jumps off of the second chamber, fire your contagion at it and melee the amoebas that appear to refill your mutagen. This is done after the second one because of the sheer numbers of Black Ops that you fight before him may have severely drained your health. You may want to use the parasites to refill it. If this is not the case, feel free to use the contagion after he breaks the first chamber. After you use the contagion, repeat the process of melee and parasites until the monster dies. The fight should take no longer than ten minutes.
To defeat the Theta easily, first make sure that you have a fully charged Mutagen bar and at least three quarters of your health remaining. There are health power-ups lying around where you fight it. Then, enter the room where it is as a mutant and either fire parasites or melee the Leapers that come after you. Use parasites on the first few to restore your health, then attack the rest with melee to keep your mutagen full and also leaves the health power-ups available if needed. Try not to hit the explosive barrels as they will almost certainly kill you instantly. The Theta will appear after about four Leaper waves and leap at you. Fire a few parasites at it, then move in close to melee it. Though the Theta is both fast and strong, in your mutant form it is very easy to hit it and dodge it's attacks because of how the "mutant vision" slows him down. The only attack to worry about is its jump attack that will cause almost fatal damage, even with the damage reduction of mutant form. If you repeat this process (attacking the Leapers with melee or the parasites when they appear) you will defeat the Theta fairly quickly and still have plenty of health and mutagen remaining for the next level.
A good way way to defeat the Theta is to first mutate. Next, fire parasites; or if you want to take a chance, fire contagion to lay some heavy damage on him. Note: Use contagion for heavy damage, but parasites also work well, especially because they heal you. When your mutagen runs low, run up and melee him and/or the enemies he releases on you (the "bubbles" or leapers). Keep doing this and he will eventually go down. This will take some time to accomplish and may be difficult at first.