On the other hand, molecules with lower dipole moments may present challenges for detection requiring specific observational conditions. By providing detailed spectroscopic data, including rotational constants and dipole moments, this study establishes a valuable resource for targeting molecules in subsequent observational studies. The findings not only highlight the significance of dipole moments for astrophysical searches but also contribute to refining detection strategies for complex organic molecules in the ISM and CSE. -288.645243 0.00 b For relative energies (kcal/mol), the zero of energy is assigned to the lowest-energy conformer. c Only the molecules with the number of atoms less than 7 are calculated with both DFT and CCSD(T). We introduced a new methodology to explore possible ISM and CSE molecules that combines ML, general principles from chemistry and astrophysics, and quantum chemical calculations. The proposed approach enables screening of thousands to millions of potential interstellar reactions within a computationally feasible timeframe (e.g., several days) while maintaining high predictive accuracy. By combining ML techniques with quantum chemical calculations, this methodology addresses the challenge of identifying undetected interstellar molecules.