<p>Water/alcohol-soluble organic luminophores are a crucial subclass of luminescent materials that uniquely enable biomedical applications and eco-friendly optoelectronics that are inaccessible to their conventional hydrophobic counterparts. This review systematically outlines two fundamental strategies for achieving this essential solubility: chemical modification through covalent functionalization and physical encapsulation <i>via</i> supramolecular assembly. We analyzed the inherent trade-offs of each approach in terms of stability, luminescence properties, and synthetic complexity. Subsequently, we trace the evolution of these design principles across three major classes of luminophores: fluorescent, phosphorescent, and thermally activated delayed-fluorescence systems. Furthermore, we highlight their transformative applications in bioimaging, biosensing, anti-counterfeiting, and sustainable electronics. By mapping these strategies and applications, this review underscores how solubility design paves the way for broader utilization of organic luminophores in cutting-edge luminescent technologies.</p>