In 2026, Spaceflight Associated Neuro-ocular Syndrome (SANS) is still one of the biggest obstacles in the future of space exploration, and it comes with important medical risks for astronauts involved in long duration missions. Characterized by optic disc edema, chorioretinal folds, globe flattening and refractive changes, SANS can affect up to 70% of astronauts exposed to microgravity for extended periods of time, and some of those symptoms can persist even after return to Earth. Even though there are numerous studies on different techniques for the mitigation of SANS, their effectiveness can be limited when applied in isolation, revealing the need for a comprehensive analysis of combined strategies. This paper aims to close this gap by presenting a systematic review of recent spaceflight data and analog mission studies, with the goal of unifying the current evidence and formulating more effective and integrative protocols for mitigation and prevention of SANS.Studied countermeasures include mechanical and biological approaches such as Lower Body Negative Pressure (LBNP), bilateral venous constrictive thigh cuffs, artificial gravity through short-arm centrifugation, hydrogen-rich water and 25-hydroxycholesterol (25-HC). A comparative analysis of peer reviewed studies performed in humans exposed to outer space microgravity and analog conditions is used to determine their level of effectiveness, and their capacity to work together to maximize their results. The expected outcome is a multimodal framework that integrates diverse countermeasures, predisposing factors, sex-based differences in intraocular pressure responses, lifestyle influences related to neuro-ocular health, and cost-effective early detection techniques.