Spaceflight associated neuro-ocular syndrome (SANS) refers to a unique collection of neuro-ophthalmic clinical and imaging findings observed in astronauts after long duration spaceflight. Current in-flight and post-flight imaging modalities (e.g., optical coherence tomography, orbital ultrasound, and funduscopy) have played an instrumental role in the understanding and monitoring of SANS development; however, the precise etiology for this neuro-ophthalmic phenomenon is still not completely understood. SANS may be a potential barrier to future deep space missions, and therefore it is critical to further elucidate the underlying pathophysiology for effective countermeasures. The complexity and unique limitations of spaceflight require careful consideration and integration of leading technology to advance our knowledge of this extraterrestrial syndrome. We describe the current neuro-ophthalmic imaging modalities and hypotheses that have improved our current understanding of SANS, discuss newer developments in SANS imaging (including non-invasive near-infrared spectroscopy), and summarize emerging research in the development of an aspirational future head-mounted virtual reality display with multimodal visual assessment technology for the detection of neuro-ocular findings in SANS.