Cancer is a mortal disease that can invade other parts of the body and cause severe complications. Despite their continuous progress, conventional cancer therapies including surgery, chemotherapy, and radiation therapy have their inherent limitations. To improve the precision of cancer treatment, maximize the therapeutic effect and minimize mortality, synergistic therapies combining imaging guiding technologies, phototherapy, and other therapies have emerged due to the mutually strengthening therapeutic efficacy. However, traditional organic phototherapeutic agents are limited since their aggregation in aqueous media usually affects both their luminescence behavior and therapeutic effect. In contrast, aggregate-induced emission luminogens (AIEgens) provide an ideal solution to develop phototherapy with bright fluorescence and a significant treatment effect in the aggregate state. Combining AIE-based phototherapy and conventional therapies benefits from synergistic effects and extends the potential of developing accurate cancer therapy. AIE-based synergistic therapy has been popularly discussed with such unexplored potential in recent years. This review will introduce the most recent progress of AIE-based synergistic cancer therapy.