Space Opera is a time-honored genre with vast open space, but most characters are either aliens or standard humans, maybe somebody has a prosthetic limb or two but generally augmentation is frowned upon.
It shouldn't be too surprising that eventually somebody decided to combine the two.
Compare Transhuman Aliens when transhumans substitute for aliens.
- In Strange Frame: Love and Sax, humans have moved out to the Jovian belt. In order to survive in the different environments of the Jovian moons, most humans have undergone some degree of genetic or cybernetic modification.
- The Culture is a civilization spanning a good chunk of the galaxy whose citizens engage in frequent body-modding ranging from drug glands to extra limbs to brain backups.
- Eldraeverse: The Eldrae were transhuman to begin with, being Transplanted Humans genetically modified by Precursors. Around the time they started venturing out into space they were taking things further such as adding Body Backup Drive to their "natural" lack of aging.
- Great Ship: Humanity, who for the most part have starting replacing their brains with ceramic hardware, was the first species to gain access to the titular massive starship.
- Aeon 14 is by design a reconstruction of the setting. Cyborgs, Bio-Augmentation, and fully self-aware Artificial Intelligences are all over the setting, up to and including known cases of AI merging with humans and organics and AI ascending beyond flesh and silicon. At the same time though, they still have recognizably human personalities, behaviors and motivations, and love, hate, fight, laugh and cry.
- In the Takeshi Kovacs series, Earth humans have colonized several star systems by uploading their brains to cloned bodies, often with biological or cybernetic enhancements.
- Very lightly touched upon in Crest of the Stars. While the Abh themselves play the part of Transhuman Aliens the novels mention that even more heavily modified groups exist but are generally fairly reclusive. The only non-Abh modified character we meet is a United Mankind intelligence agent who is descended from a group that modified themselves for extended lifespans.
- The GURPS setting Transhuman Space takes place in the year 2100 in a solar system colonized by genetically engineered humans, Artificial Humans, and AI.
- Eclipse Phase: During a Singularity gone wrong, Earth was evacuated by Brain Uploading to artificial bodies produced throughout the solar system.
- Hc Svnt Dracones: After a nuclear war on Earth the corporate colonies on Mars repopulated the solar system with genetically engineered human-animal hybrids and Ridiculously Human Robots. 700 years later there are entire Mega Corps specializing in Bio or Cyber augmentation.
- Nova Praxis: A seed AI known as "Mimir" provided the nanotechnology both to convert a human brain into a synthetic neural network and to build stargates.
- Mindjammer: Ten thousand years after launching STL colony ships Earth develops FTL travel and the planet's immortal oligarchs reach out to the various branches of humanity scattered throughout the stars.
- Downplayed in Always Human where Bio-Augmentation "mods" are ubiquitous, humans are beginning to colonize the solar system, and space travelers get a suite of specialized mods to acclimate themselves to off-world conditions as a matter of course.
- Orion's Arm is a future history where, over the course of the next ten millennia, humanity branches off into millions of modified clades, creates countless varieties of AI, and uplifts seemingly every species on Earth and many other planets within a 5,000-light-year radius of Sol.