Once the aerospace medical evaluation of a space flight participant has been fully considered and completed, attention can be turned to the types of evaluations that permit personalization. While there are numerous clinical, physiologic, and other measures that can be used to personalize care, there is a unique value to understanding the molecular landscape that is part of each individual. This is because the genotype and molecular phenotype represent the underlying processes that give rise to the clinical and physiologic phenotypes typically being measured in the clinical setting. This molecular landscape is comprised of the genome, epigenome, proteome, metabolome, exposome, and microbiome. In this chapter, we explore the rationale behind understanding this molecular landscape, with particular attention to essential inputs, conditionally essential inputs, and nonessential inputs. These represent actionable markers that can be used to add precision to the countermeasures applied before and after space flight.