Measurements of rovibrational spectra of clusters provide physical insight only if spectral lines can be assigned to pairs of quantum states, and further insight is obtained if one can deduce the quantitative energy-level pattern. Both steps can be so difficult that some measured spectra remain unassigned, one example is orthoH2-CO. To extend the scope of spectroscopic insights, we propose to use theoretical information in interpretation of spectra. We first performed high accuracy, full-dimensional calculations of the orthoH2-CO spectrum, at the highest practically achievable levels of electronic structure theory and quantum nuclear dynamics. Then, an iterative, theory-guided method developed here allowed us to fully interpret the spectrum of orthoH2-CO, extending the range of van der Waals clusters for which spectroscopy can provide physical insights.