Abstract: Capturing the dynamics of electronic excitations in realistic systems containing more than a few electrons is one of the outstanding theoretical challenges. Dynamical quantum fluctuations mediate interactions among excited electrons (and holes), determining the material electronic structure and optoelectronic response. A predictive ab-initio theory is critical for understanding, predicting, and designing novel compounds with tailored (quantum) properties. In this talk, I will discuss my group's developments tackling the first-principles description of excitation dynamics in molecular and condensed systems containing up to several thousands of electrons. We employ the concept of downfolding - ``lossless'' compression of the (otherwise intractable) many-body problem on an effective few-body problem solved by a combination of real-time evolution of quantum fluctuations and statistical correlators. I will exemplify these approaches in practical applications to molecules and quantum materials, e.g., exploring the correlated phenomena for localized moire states in twisted bilayer graphene and defect centers in diamond. Together with efficient low-scaling numerical techniques, it is generally applicable to (quantum) material science and chemistry problems and constitutes an ideal platform for simulating complex nanoscale systems, such as molecular assemblies or materials interfaces.