The match will start with a maximum of 16 players, of which 2 players will turn into Berserk Mutants and one player becomes the Mutant Boss, Xeno.
In this mode Mutants won't be knocked back when shot at, they will just slightly freeze in place if taking too many damages. Mutants also respawn infinitely and immediately unless they get killed by melee weapons, making killing them permanently very hard. Mutants also regenerate health very fast, 1000 HP / second.
To make up with this, Soldiers get Supply Crates far more often, around 45 seconds between each wave. They also start with 240% attack power boost allowing them to deal much more damage against mutants. Each soldier infected or killed adds 10% to this power until it reaches the maximum value of 340%. At this point, remaining soldiers in the room may become the Commando by pressing "E".
Xeno vs. Commandos
As the Mutant Boss, Xeno has the responsibility to take on the Soldiers most of the time to bring victory to the Mutants. He has longer attacking range than normal Mutants, a special ability to prevent any damage to him for a short amount of time ("G" skill), and he can see where all soldiers are. He is the only one who can finish a Commando quickly with his high damage dealing attack. A left click attack will deal 2000 damage to Commando, and a right click throw 2 strikes, each deals 3000 damage.
As the "Super Hero", Commando's only goal is to exterminate all Mutants in the room without getting killed. Up to 3 commandos can appear (In a room with 16 players), and they are armed with Dual Kukri, which can make quick works on any normal Mutant. Commando starts with 7000 HP and they can't be mutated, only be killed. Together with Mutation vest, Commandos are quite dangerous when grouped together. However, Commandos still move slower than the mutants, so they could get surrounded and outnumbered easily.
- Because mutants won't get knocked back, remember to back down while shooting at them. Standing in place is not an option unless you have companion defending with you. It's also recommended to use MGs for defense and SMGs for hunting. Gatling Gun isn't recommended unless you know that your team can help defend you. Shotguns (advisably semi-auto) is also useful for hunting. Rifle will be useful if players pack with enough spare ammunition. Sniper is not recommended (though Barrett M82A1 & its variant are useful).
- Pistols are not useful for engagement at all but will provide enough help as backup (when primary weapons are empty). Desert Eagle Born-Beast, Desert Eagle-El Dorado and Mauser M1896 (and its variant) are considerably useful for backup.
- Bio Grenade deals a very large amount of damage, so don't waste it so quickly. Keep it until the very last moment you can or at least when 3 or more mutants are close together. You can score 4-5 kills easily with one good throw.
- To truly beat the mutants, you must kill them with any melee weapons. Shoot until they flash red, switch to your melee, then quickly slash them to death. This will reduce the number of mutants in the room, allowing you to defend longer. This can also apply to Xeno or Havoc.
- Kill the high level mutants first because they have high HP than the normal one and when they respawn, their level will be back to Level 1.
- Shoot Xeno or Havoc when they getting point from the body because when they respawn, the level doesn't disappear.
- Kill Xeno or Havoc when you have a chance. His primary attack can take 6000 HP from you.
- When there is only a few mutants left, players can go hunting them down for extra points or finish them off with melee to finish the round (though it is an option to stand on their guard until time is up as mutated players will hide somewhere & come out surprisingly to infect surviving players, which will cause panic to the rest of surviving players). If Xeno or Havoc is still alive, players should do enough precautions (standing on guard 'til time is up is recommended).
- Forget about knockback-reduction item, it won't help much in this mode.
- Use backward bunny hop to reach soldiers, this prevents them from shooting your head and limit knockback effect. Try to combine with left-right strafing to confuse them even further.
- Don't always rely on Xeno. Two or three mutants should follow him and charge at that Soldiers. As most players will focus on Xeno, you will get some rooms to get close enough to mutate them.
- Remember that you won't get knock back - try to ambush soldiers at corridors, staircases, corners... Even if they shoot at you, you should still be able to mutate them.
- Watch out for melee attacks from other soldiers. While you are charging toward a group, someone could sneak up on you and slash your head, and with luck, he could get the finish blow, thus sending you to Observation Seat.
- If you get melee challenged by someone and you know you could get killed (i.e someone with a Kukri or Shovel and he may still have mutant vest), try showing yourself to the other soldiers. Most of the time they will shoot you dead and you can respawn and try again.
- When HMX was first released, a glitch occurs that allow soldiers to score grenade kills as Mutants. If a player throws a grenade toward other soldiers and then become Mutants (After the countdown or get infected), the grenade will kill other soldiers because that player is now on the Mutants side. This was fixed in subsequence patch.
- The soldiers are completely invincible during the timer countdown (Even falling damage is disabled). If a soldier gets killed due to map glitch, the attack power boost will go up 10% as if they were infected, and the player appears as a mutant.
- This was later changed so that if a soldier gets killed, he/she will respawn as a mutant. It's most likely a glitch.
- If you throw Bio Grenade before becoming Commando and kill mutants with it, they won't appear any longer. This is because any kills as Commando is considered permanent, and the game can't tell the difference of a grenade kill and melee kill at that moment.
HMX Expansion Pack
Newer maps starting with Amusement Park and Seaside Hotel released for HMX feature new exclusive characters - Ranger and Havoc. They are the equivalent of Commando and Xeno, but with different weapons and performance.
Additionally, the variant, Ghost Vs Mutants, also use Ranger and Havoc.
- Main article: Parasite Expansion