With the advent of next-generation multi-messenger observatories, multi-messenger events will offer unprecedented opportunities to address profound questions in black hole physics, heavy element nucleosynthesis, jet dynamics, cosmic expansion, and the origin of high-energy particles. Yet, the enormous dynamical range separating the black hole from the emission region has posed significant challenges for theoretical models seeking to connect observations with underlying physics. I will present the first 3D neutrino-general relativistic magnetohydrodynamic simulations that bridge this gap. I will demonstrate how combining these large-scale simulations with analytic modeling and observational data marks a first step toward transforming time-domain astronomy by:

1. Interpreting observations from first principles - for example, resolving long-standing mysteries in gamma-ray burst observations;
2. Utilizing observational data to probe extreme physics, such as the natal properties of black holes and the engines powering the universe’s most luminous explosions; and
3. Predicting new, detectable multi-messenger sources, including kilonovae and gravitational waves from accretion disks in collapsing stars.

This integrated approach sheds new light on transient observations and sets the stage for transformative discoveries in multi-messenger astrophysics.