Polyoxometalates (POMs) as a kind of molecular metal-oxide cluster with precise chemical composition and architecture have been demonstrated to show potential in multidisciplinary materials. Accompanied by their bioactivities, POM clusters have also been shown to be capable of sensing diseases and allowing synergistic therapy based on their redox and near infrared absorption. In parallel with metal nanoparticles and organic materials, these inorganic clusters have also displayed unique photothermal imaging and therapeutic properties over recent years. In this review, we outlined the main achievements of POMs in the fields of bio-detecting probes and the photothermal effect. Fluorescence detection, magnetic resonance, computed tomography, and photothermal property-supported photoacoustic imaging acting as a multifunction platform that integrates photothermal therapy (PTT) were discussed at the same time. The comparison of nanocomposites to POMs alone in imaging-guided PTT, multi-modal imaging, and the combination of PTT with controlled chemotherapy and gas therapy were described in detail. The advantages and possible drawbacks of POMs as well as perspectives in related areas were analyzed, which ascertained such clusters to be a type of promising agent in biomedical applications.