At the Two Frontiers Project (2FP, https://twofrontiers.org/), our mission is to use bleeding-edge scientific approaches to microbially explore the two greatest frontiers facing humanity: the oceans and space. Via expeditions to the most geochemically unique ecosystems on the planet, we are building a “living database:” across thousands of unique environmental samples, microbial consortia, and biotechnologically-relevant microbial isolates, all paired with the latest DNA sequencing methods and rigorous machine-learning, genomic, and metabolic analyses. Notability, the 2FP sits at the intersection of applied research, cutting-edge methods development, and commercial opportunity. Our framework is scoped to become a next-generation scientific engine, interrogating moonshot ideas not typically funded by traditional, conservative mechanisms, and spinning them out into commercial enterprises when the technologies are fully scalable.