The possibility to achieve charge-to-spin conversion via Rashba spin–orbit effects provides stimulating opportunities toward the development of nanoscale spintronics. Here, we use first-principles calculations to study the electronic and spintronic properties of Tl₂O/PtS₂ heterostructure, for which we have confirmed the dynamical stability by its positive phonon frequencies. An unexpectedly high binding energy of −0.38 eV per unit cell depicts strong interlayer interactions between Tl₂O and PtS₂. Interestingly, we discover Rashba spin-splittings (with a large α_R value) in the valence band of Tl₂O stemming from interfacial spin–orbit effects caused by PtS₂. The role of van der Waals binding on the orbital rearrangements has been studied using the electron localization function and atomic orbital projections, which explains in detail the electronic dispersion near the Fermi level. Moreover, we explain the distinct band structure alignment in momentum space but separation in real space of Tl₂O/PtS₂ heterostructure. Since two-dimensional (2D) Tl₂O still awaits experimental confirmation, we calculate, for the first time, the Raman spectra of pristine Tl₂O and the Tl₂O/PtS₂ heterostructure and discuss peak positions corresponding to vibrational modes of the atoms. These findings offer a promising avenue to explore spin physics for potential spintronics applications via 2D heterostructures.