The game has the player develop mock assembly language code to perform certain tasks on a fictional, virtualized 1970s computer that has been corrupted.

[4] TIS-100 was based on an idea that Zach Barth, the founder and lead game designer of Zachtronics, had years prior.

The concept was named The Second Golden Age, which was set in the Middle East sometime in the near future, in which the player would program nanobots to be injected into the player-character's blood as to be able to solve various types puzzles akin to Myst.

However, he had completed the assembly-language puzzle aspect, and decided to go ahead and refine only that portion as a full game.

They used concepts from a Mondo 2000 infographic based on cybertech fashions to write the tongue-in-cheek narrative for the game and manual.

Barth stated that he took a similar approach to Early Access as with Infinifactory, providing a game that was nearly complete to gain suggestions and improvements and the ability to add more content before releasing the final product.

[8] A mobile port published by Metaversal Studios featuring twenty levels titled TIS-100P was released exclusively for iPadOS on January 8, 2016.

[9] In its article "Can Videogames Teach You Programming", Rock Paper Shotgun called the game's technology "relevant" and said "if you can survive its stiff challenge, you’re ready to code".