Sustainability science seeks to extend scientific investigation into domains characterized by a distinct problem-solving agenda, physical and social complexity, and complex moral and ethical landscapes. In this endeavor, it arguably pushes scientific investigation beyond its usual comfort zones, raising fundamental issues about how best to structure such investigation. Philosophers of science have long scrutinized the structure of science and scientific practices, and the conditions under which they operate effectively. We propose a critical engagement between sustainability scientists and philosophers of science with respect to how to engage in scientific activity in these complex domains. We identify specific issues philosophers of science raise concerning current sustainability science and the contributions philosophers can make to resolving them. In conclusion, we reflect on the steps philosophers of science could take to advance sustainability science.