This work poses and partially explores an astrobiological hypothesis: might polymeric sulfur and phosphorus-based oxides form heteropolymers in the acidic cloud decks of Venus’ atmosphere? Following an introduction to the emerging field of computational astrobiology, we demonstrate the use of quantum chemical methods to evaluate basic properties of a hypothetical carbon-free heteropolymer that might be sourced from feedstock in the Venusian atmosphere. Our modeling indicates that R-substituted polyphosphoric sulfonic ester polymers may form via multiple thermodynamically favorable pathways and exhibit sufficient kinetic stability to persist in the Venusian clouds. Their thermodynamic stability compares favorably to polypeptides, whose formation is slightly thermodynamically unfavored relative to amino acids in most known abiotic conditions. We propose a combined approach of vibrational spectroscopy and mass spectrometry to search for related materials in Venus’s atmosphere but note that none of the currently planned missions are well suited for their detection. While predicted Ultraviolet–Visible spectra suggest that the studied polymers are unlikely candidates for Venus’s unidentified UV absorbers, the broader possibility of sulfuric acid–based chemistry supporting alternative biochemistries challenges the traditional carbon-centric models of life. We argue that such unconventional lines of inquiry are warranted in the search for life beyond Earth.