Mew-Genics was initially announced by Team Meat in October 2012 as their follow-up to their critical and commercial hit, Super Meat Boy. The game was described as a "cat lady simulator", with inspiration drawn from The Sims, Pokémon, Animal Crossing and Tamagotchi. Mew-Genics would feature players managing a household of randomly-generated cats, with unique visual aspects, states of being, sizes, animation sets, statistics and personalities. The cats would breed, with their attributes averaging out to create new variants, to compensate for their aging and dying predecessors. The cats would engage in combat, heavily inspired by Pokémon.
Despite the game being featured in a playable state at conventions such as PAX Prime 2013 and PAX East 2014, Mew-Genics was hit with a number of delays, stemming from differences in priorities & interests between Team Meat's co-owners, Edmund McMillen and Tommy Refenes. Team Meat indefinitely shelved Mew-Genics in February 2016 and in 2017, McMillen departed from the company.
In January 2018, McMillen announced that he had acquired the rights to Mew-Genics from Team Meat and would be working full-time with his collaborator Tyler Glaiel, following their work together on The End is Nigh. Aside from the original soundtrack produced by Rediculon - a band featuring Matthias Bossi & Jon Evans - the game would be started completely from scratch. While McMillen was committed to completing a handful of prior projects, Glaiel began full-time work on Mew-Genics in May 2019, beginning with the development of a new engine. Several different forms of gameplay were approached, such as real-time strategy, before it was decided that a turn-based system would be ideal.