Space exploration exposes astronauts to the unique environment of microgravity, which poses significant health challenges. Identifying biomarkers that can predict an individual's resilience to the stressors of microgravity holds great promise for optimizing astronaut selection and developing personalized countermeasures. This narrative review examines the principal health risks associated with microgravity and explores potential biomarkers indicative of resilience. The biomarkers being evaluated represent a broad spectrum of physiological domains, including musculoskeletal, neurological, immunological, gastrointestinal, cardiovascular, and cutaneous systems. Earth-based microgravity analogs, such as dry immersion and head-down tilt bed rest, may provide valuable platforms to validate candidate biomarkers. However, biomarker sensitivity and specificity must be further evaluated to ensure efficacy and reliability. Establishing a panel of biomarkers predictive of resilience to microgravity-induced health risks would significantly enhance astronaut health and mission success, especially for long-duration exploration missions. Insights gained may also translate to health conditions on Earth characterized by reduced physical activity and mechanical loading.