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Below you'll find 40 prompts for full campaigns or short quests. It depends entirely on how you flesh them out. These are focused mostly on space and related themes. A different article will focus on different aspects of sci-fi in the future.
In the meantime, there's also a list of 40 campaign prompts more oriented to fantasy medieval settings, but they can be adapted to sci-fi as well. At the very least they could offer some inspiration, you can find it by clicking here.
1. A distant, Earth-like planet was colonized hundreds of years ago. Today, strange creatures emerge from caverns deep beneath the planet's surface. They want their planet back.
2. Reports come in of the destruction of a large battle cruiser part of the most technologically advanced faction. Nobody knows what happened exactly, but the ship's remnants are drifting unguarded in outer space. A small window of opportunity has opened for all those seeking to gather the ship's powerful technology for themselves.
3. Alien visitors arrive at Earth and offer their services: they will genetically enhance humans for a fee, similar to plastic surgery. Some humans gladly accept the offer, others refuse. The division becomes ever greater, with potentially disastrous results.
4. Lifeforms on nearby planets seem to be changing; it's unclear what the cause is. Mutations happen, but never this fast. Something unnatural is afoot.
5. A powerful fleet of ships has arrived at Earth. They seek to buy Earth and are willing to move all humans to a planet suitable to their needs as well as generously reimbursing all inhabitants. Most inhabitants have accepted the offer, but some refuse to leave.
6. A distress signal is coming from outer space. It's coming closer and closer, and it's soon apparent the beacon is atop an asteroid headed for Earth. It's unclear who the beacon belongs to or why it was put there.
7. The few inhabitants of a nearby moon are planning to destroy it in a self-sacrificial ritual. The destruction would have disastrous effects on the nearby planet, though there's not much life there to begin with. But this could in turn have a domino effect on other planets nearby.
8. Communications with an allied planet goes dead. The causes are unknown, but the communication technology is still working fine.
9. The consciousnesses of millions of people uploaded to the cloud over the past hundred years have become the target of a hostage situation of a large corporation. Their demands are simple: grant them the newly discovered planet or their servers will be wiped clean of all people.
10. The party returns to Earth after what seemed to be a successful mission. When they return, Earth is no more.
11. A new alien species stumbles upon the party. The party's actions will determine how these aliens see humanity as a whole and how they'll deal with them.
12. Alien visitors claim it was indeed them behind the pyramids, crop circles and other myths. This spreads division among humans, all according to the aliens' plan.
13. The party is tasked with aiding in a large-scale mission to prevent the collision of a large asteroid with an allied planet. During the mission, sabotage becomes increasingly clear.
14. A seemingly deserted ship drifts through space. Aboard the ship there are no signs of violence. Plates of food have been left half eaten, supplies seem untouched and personal belongings are left in place.
15. Once out of warp, the planet you were supposed to be headed to is instead a seemingly completely different one. All the data pointed to a specific planet awaiting your arrival, yet the reality seems to disagree.
16. Your party is tasked with delivering a routine cargo load. One of the crew, out of clumsiness or sheer curiosity, opened one of the crates. The cargo is not at all what is on the ledger.
17. While warping through space, the ship suddenly stops. Outside the ship many others drift through space, seemingly as stranded by an unknown force as the party.
18. A routine asteroid removal job reveals hidden ruins beneath the rocky surface.
19. Technologic advances in recording equipment show strange anomalies when recording many world leaders. The same doesn't happen when recording regular people.
20. Earth receives a strange message coming from the moon. It's being sent using leftover technology of the moon landing, among other things.
21. Upon arrival on a distant planet, the locals greet the party and praise their return. They seem to have built a religion of sorts around the idea the party's species was involved in enhancing this planet's population beyond what nature could've provided.
22. The party receives a coded message. Somehow it seems to come from within a star.
23. A meteorite's impact on Earth has started a shift in behavior from all beings around the crater. The effects are spreading.
24. A mission set out to divert an asteroid headed towards Earth reveals an alien species has already landed on this asteroid. They're the ones pushing it toward Earth.
25. The party stumbled upon an alien probe akin to Earth's voyager probes. There's a message on this probe too; experts contradict each other in what they think it means.
26. An alien species arrived on Earth a long time ago; they used human bodies they created to make sure they'd survive on this planet. Many years later, nobody knows for sure which humans are aliens and how many of them there are.
27. Terraforming efforts on a distant planet have grown out of hand. Everything is growing to enormous proportions, including any local fauna hidden in plain sight.
28. A robotic species arrives on Earth. They're here to judge and learn from humanity the same way they've judged and learnt from many other beings on other distant planets. Soon after a member of the species who created these robotic judges arrives to warn Earth.
29. Satellites orbiting Earth are being hijacked one by one. Every time the satellite is pointed at a seemingly empty point in space.
30. Members of an alien species arrive on Earth. They're here on a peaceful mission to share information and technology. They tell of their home planet, which human scientists manage to find. It's soon discovered, unbeknown to the alien visitors, there's no life left on it.
31. An alien species begins to settle on planets and moons around Earth, essentially preventing humanity from engaging in space colonization and expansion. The aliens claim they're free to take these planets, humans hold no ownership over them.
32. A few members of an alien species arrive on Earth and plead for humanity's help. A war is being waged and their species are being destroyed because of it. Soon after, the alien species they're at war with arrive on Earth after following the others' trail.
33. A ship is sighted coming out of a black hole.
34. A trade vessel approaches and offers part of their cargo in exchange for part of your fuel. The cargo seems innocent enough, but there's a beacon planted on it and pursuers are on their way.
35. Stars are disappearing from the sky night. The cause is unclear, but stars closer and closer to Earth are disappearing faster and faster.
36. Upon accepting alien visitors to Earth in a historical moment, disease breaks out among humanity as different lifeforms mix in unforeseen ways.
37. In exchange for security and technological advancements, an alien species seeks a hundred human beings in return. Their exact purpose for them is unclear, but they wish to pick them out themselves as to ensure they do not get "damaged or faulty goods".
38. The sun's color changes. Scientists have no clue what caused it, but something is visible behind our star.
39. Several world leaders are called out by an alien species. Some change their ways to appease these beings, others double down on being right about what they're doing.
40. A messenger vessel finds the party and delivers a package labeled with the name of one of the crew. The contents seem to be childhood items of some sort along with a message in a foreign language asking them to come back home. The rest of the crew receives similar packages later down the line, each with a similar message, but in different languages.