Massive stars are crucial building blocks in the study of star-forming galaxies, stellar evolution, and transient events, and their applications as fundamental astrophysical tools span a broad range of subfields. Unfortunately, many key traits of massive stars - from their physical properties and ionizing radiation to their evolution and core- collapse deaths - remain poorly understood. I will discuss several current research programs focused on developing a comprehensive picture of massive stars across the cosmos. These include observational surveys and population synthesis models of star-forming galaxies; progenitor and host environment studies of transient phenomena such as supernovae and gamma-ray bursts; and the remarkable reach of extragalactic stellar observations, which recently led to the discovery of the first Thorne-Zytkow object candidate. With cutting-edge theoretical models and the capabilities of current ground-based and orbital observatories, we are ideally poised to make substantial progress in our understanding of massive stars over the coming decade. This in turn will equip us with the tools we need to take full advantage of the frontiers opened up by new observational facilities such as JWST, the ELTs, and LSST, allowing us to immediately begin probing the new corners of the universe that they reveal.