Phototherapeutic strategies, particularly photothermal therapy (PTT) and photodynamic therapy (PDT), have garnered significant attention as safe, effective, and noninvasive approaches for disease treatment. The development of efficient phototherapeutic agents through the manipulation of molecular photophysical properties has emerged as a focal point in dye chemistry research. Recently, supramolecular aggregation with ordered molecular arrangements has surfaced as a promising strategy for controlling photophysical properties, offering the potential to revolutionize the field of phototherapeutics. By constructing supramolecular aggregates with diverse photophysical properties, the cost of phototherapeutic agents can be greatly reduced, and the biomedical applications of dyes can be expanded. Notably, cyanine supramolecular aggregates, characterized by their stable structures, controlled photophysical effects, and outstanding biocompatibility, have attracted extensive attention. For instance, J-aggregation contributes to the PDT effect of cyanine dyes, while H-aggregation with close strong molecular coupling significantly enhances photothermal conversion efficiency. This entry delves into the intricate relationship between molecular aggregation modes and photophysical properties, focusing on cyanine dyes as a model system. The biological applications, including PDT and PTT, enhanced by different aggregation modes, are summarized in detail. We also look forward to the future directions of cyanine supramolecular aggregates, with a central objective of revolutionizing cancer treatment through a focal emphasis on simplicity, effectiveness, and safety.