Background <p>Endotamponade selection is best understood as a physics-informed, phenotype-based decision rather than one driven mainly by tamponade duration or material class. This narrative review integrates density, interfacial tension, contact angle, viscosity, and drug–tamponade interactions with phenotype-specific clinical outcomes. The result is a practical framework linking tamponade behavior to retinal geography, disease complexity, and postoperative feasibility.</p> Main body <p>Lighter-than-water agents (air, expansile gases, and light silicone oils [LSOs]) preferentially support the superior retina, whereas heavy silicone oils (HSOs) and perfluorocarbon liquids (PFCLs) provide stronger inferior support. In uncomplicated rhegmatogenous retinal detachment (RRD) and many idiopathic macular holes (MHs), air or sulfur hexafluoride (SF₆) usually achieves high anatomical success with less early intraocular pressure (IOP) elevation and cataract burden than longer-acting gas or silicone oil when brief postoperative positioning is feasible. LSO remains the principal long-term option for complex, tractional, and traumatic disease because it provides durable, relatively posture-independent support, but at the cost of emulsification, cataract, pressure-related, and corneal complications. HSO and staged short-term PFCL are best viewed as selective strategies for inferior-predominant giant retinal tear (GRT) or posture-limited phenotypes, where the mechanistic rationale is strong but comparative evidence remains largely observational. Hydrogel-based vitreous substitutes are promising but remain investigational.</p> Conclusions <p>Current evidence supports a physics-informed, phenotype-based approach to endotamponade selection. Future research should prioritize phenotype-stratified comparative studies with standardized anatomical and emulsification endpoints and rigorous evaluation of emerging vitreous substitutes in well-defined clinical settings.</p> Trial registration <p>Not applied.</p>