Atomically thin materials based on transition-metal dichalcogenides and graphene offer a promising avenue for unlocking the mechanisms underlying the spin Hall effect (SHE) in heterointerfaces. Here we develop a microscopic theory of the SHE for twisted van der Waals heterostructures that fully incorporates twisting and disorder effects and illustrate the critical role of symmetry breaking in the generation of spin Hall currents. We find that an accurate treatment of vertex corrections leads to a qualitatively and quantitatively different SHE than that obtained from the popular iη and ladder approximations. A pronounced oscillatory behavior of skew-scattering processes with twist angle θ is predicted, reflecting a nontrivial interplay of Rashba and valley-Zeeman effects and yields a vanishing SHE for θ=30∘ and, for graphene-WSe2 heterostructures, an optimal SHE for θ≈17∘. Our findings reveal disorder and broken symmetries as important knobs to optimize interfacial SHEs. Published by the American Physical Society 2024