Innovation leaders often push for moonshot innovations that create entirely new markets for their enterprises and catapult them into new realms of revenue generation. However, many leaders don’t realize that these moonshots involve tolerating the highest risk of failure, ongoing funding, and years of uncertainty about the outcome, as well as employing the right people with the right attitude and skills. We reveal what innovation leaders can learn from NASA’s James Webb Space Telescope project about operationalizing the success factors of their enterprise’s moonshot innovations.