Quantum computers promise an exciting path to the scalable simulation of quantum matter. However, in their nascent state, the accessible gate depth of quantum computation on available hardware remains highly constrained. In this thesis, I present a suite of hybrid quantum-classical algorithms that aid Hamiltonian simulation across both the Noisy Intermediate-Scale Quantum era and future fault-tolerant architectures. By treating classical computation as an active resource to refine quantum algorithms, I develop automated, variational methods to learn hardware-efficient circuits. This work aims to overcome traditional trainability barriers, such as barren plateaus, by embedding physical symmetries directly into the circuit design. Central to the thesis is the synergistic use of tensor networks to classically pre-compute weakly entangled stages of a quantum simulation. This enables the compression of deep circuits, drastically reducing both the accumulation of gate errors on near-term physical qubits and the prohibitive overhead of operations like magic state distillation on error-corrected hardware, reserving the quantum processor strictly for the most challenging, highly entangled dynamics. These methodologies are ultimately directed toward the ab-initio simulation of subatomic physics, providing a scalable approach for the first-principles study of strongly correlated systems, including nuclear structure and lattice gauge theories.