This page is for strategies for the Smallpox scenario. Feel free to add your own strategies, tips, and Q&A below:

Strategies (by Risviltsov)

Risviltsov here! Let's get right to it! This guide is divided into four sections, each for the four difficulties.

Casual Smallpox

Here's what you need to perform to complete Smallpox on Casual difficulty.

Genetic Code

  • ATP Boost
  • Genetic Mimic
  • Aquacyte
  • Extremophile
  • Sympto-Stasis

Phase I - Hide!

Start in Saudi Arabia! Unfortunately, Smallpox has a very high starting severity and lethality, but this can be fixed! Devolve the following symptoms, I've prioritized them into which ones to devolve first.

  1. Pustules
  2. Systemic Infection
  3. Pneumonia
  4. Fever

Unfortunately, these aren't enough to be able to hide away from 100,000 infected alone. You'll also need to evolve White Pox 1.

Phase II - Infect!

You'll need to be able to infect everyone, so evolve some of these transmissions.

  • Droplets II
  • Droplets III
  • Fomities I
  • Air I
  • Air II
  • Water I
  • Water II
  • Fomities II
  • Extreme Bioaerosol

Phase III - Resist!

Your strain is very weak! (as weak as the Necroa Virus, having $9 million to defeat you) Let's make it stronger! (Evolve most of the following abilites)

  • Cold Resistance I
  • Cold Resistance II
  • Drug Resistance I
  • Vaccine Shield
  • Genetic Hardening I
  • Genetic Hardening II
  • Drug Resistance II

Phase IV - Massacre!

Once the Caribbean and Greenland has been infected, we'll need to rapidly eradicate the human population. Evolve the following, prioritized for your convenience.

  1. Systemic Infection > Necrosis > Black Pox > Haemorrhagic Shock > Internal Haemorrhaging > Total Organ Failure with Fever > Coma
  2. Systemic Infection > Necrosis > Osteomyelitis, Immune Suppression, Fever > Acute Encephalitis - Coma > Dysentery > Diarrhoea
  3. Black Pox > Haemoptysis > Purpura > Internal Haemorrhaging > Total Organ Failure - Haemorrhagic Shock and Systemic Infection

Normal Smallpox

Smallpox is only a tad more difficult when you raise the difficulty up from Casual to Normal. Here's what you need to beat it on Normal.

NOTE: Devolve any mutations unless otherwise stated.

Genetic Code

  • ATP Boost
  • Genetic Mimic
  • Aquacyte
  • Extremophile
  • Translesion +

Phase I - Hide, once again!

Start in Saudi Arabia.

We still need to hide our little strain of Variola Major. The emphasis here is that we need to do it more effectively. Devolve these symptoms immediately.

  • Pustules
  • Systemic Infection
  • Pneumonia

We need to focus on nullifying the severity and the lethality. Continue playing and do the following.

  1. Devolve Fever.
  2. Evolve White Pox 1.
  3. Evolve White Pox 2.

By now, the severity and the lethality should be at zero. Now we shall infect!

NOTE: If anything mutates and there is still no lethality or severity, leave it be. It will help us during our murderous attack at the end of this guide.

Phase II - Infect them all!

To be honest, we don't need to evolve anything, but if we don't want to lose a lot of DNA due to devolving mutations, we should at least evolve something that helps spread our disease. Evolve the following transmissions.

  • Droplets 2
  • Droplets 3

This should be enough to use planes as our primary transmission vector. We also need to fight back the soon to occur cure and we need to raise infectiousness in cold climates, so evolve the following abilities.

  • Drug Resistance 1
  • Cold Resistance 1
  • Genetic Hardening 1
  • Genetic Hardening 2
  • Cold Resistance 2


Once everyone in the world is infected, you must start killing everyone off. To start, devolve the following.

  • White Pox 2
  • White Pox 1

Now, if you can, evolve the following.

  • Black Pox
  • Immune Suppression

If you are lucky, they will not figure out your plague until 100 million people have died. This is what happened with me, but this guide still works even if that is not the case. Evolve the following to bring doom onto the world that has treated you like you were dirt!

  • Anything that increases lethality, such as Systemic Infection
  • Anything that slows down cure efforts, such as Corneal Ulceration
  • If at any point the cure is at an uncomfortable progress, evolve Genetic ReShuffles or evolve something that slows down cure efforts.

Here is what my results were:

  • Score Total: 29,312
  • Time: 747 days
  • Cure: 72% complete

Strategies (by Troubledsoul25)

Instead of going 'sneaky-beaky' like most people would think, I choose more aggressive approach on this disease, exploiting its high initial infectivity and lethality. Tested on both Normal and Brutal difficulty with 2 biohazards guaranteed.

Genes required

How to play

  1. Start in India.
  2. Evolve Droplets 2 and 3.
  3. After you infected few people, they may already notice the disease, but don't worry, this was expected.
  4. Evolve Vaccine Shield as soon as they start vaccination programme. Pay attention to the news or infected count. If it is decreasing then the vaccination program is already begun.
  5. Evolve Drug Resistance 1, Genetic Hardening 1 and2, and Cold Resistance 1.
  6. Evolve Fomites 1, Water 1 and2, Heat Resistance 1 and 2, and Environmental bring the plague worldwide faster.
  7. At this point, you might want to slow down the time, as the plague spread to countries really fast you might miss some of those red bubbles.
  8. Evolve Necrosis, Corneal Ulceration, Coma, and the remaining vaccine shields. Don't worry about your plague killing faster than infecting. Its infection rate is always faster than its death rate.
  9. Evolve Fomites 2, Air 1 and 2, Extreme Bioaerosol, and Cold Resistance 2.
  10. Evolve some symptoms to increase the lethality.
  11. If the cure progress is worryingly high, evolve Genetic Reshuffles.
  12. When every country in the world is infected, then that's it, you won!

Here are my results :

Normal :

  • Score Total : 55,197

Time : 387 days

  • Cure progress : 80% complete

Brutal :

  • Score Total : 52,914
  • Time : 390 days

Cure progress : 90% complete

Strategy for Mega Brutal (by 雪沫乳花) (Mobile only)

Translated by Bihapove

Smallpox gets significantly harder on Mega Brutal because of the increased research rate. Also, islands shut their ports faster than on lower difficulties.

Thus, you might need to invest more on Transmissions and Abilities (especially Genetic Hardening). The result is fewer DNA points invested in Symptoms. So, in this strategy I choose to evolve NEITHER White Pox NOR Black Pox. The initial lethality is almost all we need.

Certain events can be disastrous. For example, if an Awareness Day takes place at early game, don't hesitate to restart.

* This strategy is risky on PC due to the increased research rate and lethality. --Bihapove

Genetic Code

  • ATP Boost
  • Genetic Mimic
  • Suppresion
  • Urbophile
  • Patho-Statis

Start in China.

  1. Evolve Fomites 1 immediately after you start
  2. Click the first Biohazzard Bubble when it's about to disappear. Severity has climbed at this moment, so you should receive 3 DNA points instead of 1.
  3. Evolve Vaccine Shield.
  4. Evolve Air 1, Water 1 and Water 2. This can help you infect wealthy countries quickly. An uninfected one in late game can be a HUGE problem!
  5. Evolve Drug Resistance 1, Genetic Hardening 1 and Genetic Hardening 2.
  6. Evolve Cold Resistance 1 and 2.
  7. Evolve Drug Resistance 2, Heat Resistance 1 and 2.
  8. Check the news box frequently for new Experimental Vaccines, and evolve the relevant Vaccine Shield. Alternatively, you can just evolve all three in a row.
  9. Evolve Necrosis.
  10. Evolve Environmental Hardening.

Note: This is where most of my runs fail on PC.

  1. Evolve Livestock 1, Livestock 2, Air 2, Droplets 2 and Droplets 3.
  2. Evolve Coma.
  3. If cure is too high, evolve Genetic ReShuffles.
  4. Welcome to 3 Biohazzards on Mega Brutal difficulty.

Strategy for Mega Brutal (PC Mega Brutal 3 Biohazzards)

Genetic Code

Throughout the whole game, these events greatly reduce your success rate and score. If any of them happen, get ready for a loss.

  • Awareness Day -- greatly speeds up cure, very likely to happen due to high initial severity
  • Threat Level Increase -- greatly speeds up cure
  • Any environmental debuffs. Example: Cold countries getting colder -- slows infection
  • Fear Slows Economy -- slows cross-country infection
  • India shutting down airports/ports unusually early -- slows infection
  • Genes manipulated / Fully sequenced -- slightly speeds up cure
  • Executing infected / Bombing cities -- significantly slows infection in a country

Frequent Save/Load is required, which sometimes confuses the system (idk why). If your save file 'disappears', reboot Plague Inc. Evolved.

Start in India.

  1. Wait until the red bubble almost disappears, then collect it.
  2. Evolve Heat Resistance 1.
  3. Once you are detected, evolve Vaccine Shield. If vaccination program begins before you have enough DNA points (unlikely), restart.
  4. Evolve Fomites 1, Water 1, Water 2, Air 1 and Fomites 2.
  5. Evolve Corneal Ulcernation.
  6. Evolve Drug Resistance 1, Genetic Hardening 1 and Genetic Hardening 2.
  7. From this point on, you must frequently check the news box for new Vaccines. If any pops up, evolve the corresponding Vaccine Shield.
  8. Evolve environmental resistance upgrades until you have Cold, Heat and Drug Resistance 2.
  9. Evolve Environmental Hardening, then Extreme Bioaerosol. Islands have started shutting down ports. Try to save your game after any island country is infected.
  10. Evolve Necrosis.
  11. Evolve Vomiting, Diarrhoea, Dysentery and Hyper sensitivity.
  12. Evolve Coma. You should have only 1 or 2 uninfected islands now. If they shut down their ports, please load your save files.
  13. If cure is too high (95%+), evolve Genetic ReShuffles.
  14. Consider Livestock 1 or Blood 1 if your virus struggle in certain regions.
  15. If you have plenty of DNA points, evolve Black Pox, Subconjunctival Bleed and Purpura.
  16. Spend all your extra points in Genetic ReShuffles.
  17. If nothing went wrong, you should end up with 65000+ score.

This can be tricky and luck-based. Don't lose your heart.

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