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Environmental conditions fundamentally shape host-pathogen interactions; however, how multiple extreme abiotic stressors combine to influence infection outcomes remains poorly understood. All living beings have evolved under specific gravitational and radiation regimes; deviations from these conditions-whether in extreme terrestrial environments or beyond Earth-may alter physiological homeostasis, including immune function and pathogen replication. In this study, we investigated the effects of reduced gravity and lowered muon flux on Orsay virus infection in the nematode <i>Caenorhabditis elegans</i>. We employed a fully factorial experimental design, examining how each factor, alone and in combination, influences fecundity and developmental traits and viral load. While below-background radiation radically affected viral accumulation dynamics, reduced gravity had a minor effect. Both factors significantly impacted reproduction and morphology, with some effects magnified by viral infection. These results reveal how even partial modifications of Earth-like gravity and radiation levels can alter host-pathogen interactions. By integrating experimental observations with mathematical modeling, we suggest that these environmental stressors may primarily affect prezygotic reproductive processes and modulate viral replication through distinct and sometimes antagonistic mechanisms. Although this work does not encompass the full complexity of space environments, where cosmic radiation includes high-energy protons and heavy ions, it provides insight into how adjustable models of reduced gravity and radiation can advance our understanding of biological adaptation beyond standard terrestrial conditions.IMPORTANCEUnderstanding how extreme environmental conditions affect host-pathogen interactions is critical for exploring fundamental principles of stress biology. This study demonstrates that reduced gravity and diminished muon radiation flux can significantly alter viral infection dynamics and host physiology in <i>Caenorhabditis elegans</i>. By integrating experimental data with mathematical modeling, we propose that these abiotic stresses impact prezygotic reproductive processes and modulate viral replication in distinct and sometimes antagonistic ways. Our findings suggest that even partial deviations from Earth-like conditions can reshape infection outcomes and developmental trajectories, highlighting the need for deeper mechanistic insights into biological adaptation beyond terrestrial norms. These results have implications for space biosciences, evolutionary virology, radiation hormesis, and the design of countermeasures to preserve organismal health in extreme or non-terrestrial habitats.