Cancer is still among the leading health issues today, considering the cost, effectiveness, complexity of detection/treatment modalities and survival rates. One of the most important criteria for higher survival rates is the early and sensitive diagnosis of the disease that can direct the treatment modalities effectively. Fluorescence imaging agents emerged as an important alternative to the current state of the art due to their spatial and temporal resolution, high sensitivity and selectivity, ease of modification towards generating activatable agents, ease of operation, and low cost. In addition to imaging, light-based treatment modality, photodynamic therapy (PDT), attained remarkable attention, as it is minimally invasive and has fewer side effects compared to the current standard of care treatments. Even though fluorescence imaging and PDT have these significant advantages, light that needs to excite the agent has limited penetration in tissues, hindering widespread utilization. Hybrid xanthene dyes, particularly ones bearing silicon or phosphine oxide as the bridging unit of xanthene moiety, gained significant interest not only due to their excellent photochemical properties in aqueous media, high fluorescence quantum yield, photostability but also their proper absorption and emission maxima that allow for deep tissue imaging and therapy. Here, the design and synthesis strategies, key photophysical properties, their application in fluorescence imaging applications, and surprisingly limited utilization as PDT agents of hybrid xanthene dyes that emerged in the last decade have been reviewed in detail.