Plague Inc. Bio-Weapon Mega-Brutal Guide/ Walkthrough/ Strategy

Beating Bio-Weapon in mega-brutal difficulty isn't exactly as difficult I thought it would be, but getting 5 biohazards on it is. It's unique ability to boost lethality to the maximum is probably the main reason why I found this plague easy to beat even at mega-brutal difficulty.

All through-out the game you'll be forced to keep an eye on deaths because you really don't want to let the Bio-Weapon gain more and more lethality. Letting it do so will make it impossible to infect new countries. My strategy here is does just that, keep the bio-weapon's lethality at a minimum while infecting the whole world then letting it unleash hell near the end. That being said, the hard part starts at the beginning and the end will just be watching countries pile up the corpses.

Because of the randomness of the increases of lethality, you'll need to keep an eye on the dead count at the bottom of the screen. If you notice people dying, you'll need to immediately evolve one of bio-weapon's unique abilities, which is Deactivate Modified Genes. This ability has three stems and we'll be using them every time the plague starts killing people.

The best biohazard score I had by using this strategy is a 4, and always a 4. I couldn't get a 5, sorry for being a "noob". If I ever find a strategy that almost always gets a 5 Biohazard score, I'll be sure do update this guide. But for now, you're stuck with this one so let's begin.

Gene Setup:

  • ATP Boost
  • Aquacyte
  • Patho-Stasis
  • Genetic Mimic
  • Extremophile
1.) Before selecting a country to start in, evolve Gene Compression 1 and 2

2.) Start in India then evolve Gene Compression 3 and Deactivated Modified Genes 1 as soon as you have the DNA.

3.) From here on, if your plague starts killing people evolve Deactivated Modified Genes 2. If it starts killing again, evolve Deactivated Modified Genes 3. Continue to evolve the next set of symptoms, transmissions, and abilities.

Evolve the following symptoms and devolve anything that mutates:
  • Coughing
  • Pneumonia
  • Sneezing
  • Cysts
  • Hyper Sensitivity
  • Abscesses
Afterwards, evolve these transmissions and abilities in this order:
  • Water and Air 1 and 2
  • Extreme Bioaerosol
  • Drug Resistance 1 and 2
  • Cold Resistance 1 and 2
  • Heat Resistance 1 and 2
  • Environmental Hardening
  • Genetic Hardening 1 and 2
  • Nucleic Acid Neutralisation 1, 2, and 3
4.) Wait until the entire world is infected, then evolve Unlock Annihilation Gene.(Hurray for max lethality! People will drop like flies.)

5.) Remaining DNA should be used to evolve the following:(get them in this order. It is not necessary to evolve all of them)
  • Genetic Reshuffles 1, 2, and 3
  • Paralysis
  • Coma
  • Insomnia
  • Paranoia
  • Seizures
  • Insanity
That about does it, now just wait and watch the world get rid of humans.

As I stated before this guide, I only got a 4 biohazard score using this strategy. So if you guys have any tips or strategies better than this one(better if it gets 5 biohazards), please share them with us. Post them at the comments below and I'll include the good ones I test out along with this guide. Happy Spicy Gaming!

Alternate Strategies


  1. Hi there. I got a 5/5 using your guide, but I didn't evolve anything after coma, and I actually let not-so-lethal symptoms mutate freely. Was able to do this 2/2 times.

  2. Great strategy. Works really fine.
    427 Days
    18% Cure
    4 Biohazards

  3. 4/5 507 days, 1st time. 50% cure however. But this was due to coma late due to drifts.

  4. Really nice strategy, but some of this may come handy, but need testing.
    -Don't devolve symptoms unless really needed(total organ failure), you only wasting DNA on reduction of infectivity
    -Heat resistance not really necessary(but i know its cheap with patho-stasis)(not tested)
    -Lethality when already infected lots of countries can help you get DNA and stops cure

    Let me know if it helped.(im not a hardcore player, i got experience, but not much in megabrutal)

  5. I am so grateful for these strategies! I can sit for days totally frustrated at this game lol.

  6. I infected the world too fast and got cured before I had the DNA to kill people.

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  9. I don't get it. I followed your strategy EXACTLY and I still got cured... Maybe I just suck at video games, but I've beaten every other disease type on Mega-Brutal, but Bioweapon kicks my butt.

  10. Works 100% perfectly and also, is so easy! Here are my results:
    34% Cure
    356 Days
    5/5 Biohazard

  11. Doesn't work. Greenland closes its borders every single time.

  12. Proof of this strategy in action: