Metal oxide nanomaterials have exhibited excellent performance as nanomedicines in photodynamic therapy (PDT) for cancer and infection treatment. Their unique and tunable physicochemical properties advance them as promising alternatives in drug delivery, early diagnosis, imaging, and treatment against various tumors and infectious diseases. Moreover, the implementation of nanophototherapy in deep tissue sites is enhanced by advancements in photosensitization technology. Notwithstanding the progress made in emerging metal oxide nanomaterials-derived PDT, the potential toxicity towards adjunct tissues associated with this approach remains challenging. Regulation and legislation have also been recommended and subsequently enacted in response to public concerns related to large-scale production, transportation, use, and disposal of those nanomaterials. Consequently, a quantitative structure-activity relationship (QSAR) paradigm has been adopted and is widely used in evaluating and predicting the side effects of nanomedicines, thus influencing their design and fabrication. This article briefly reviews the application of metal oxide nanomaterials in PDT and their associated adverse impacts as reported in recent publications. The future trends and implications of this platform in nanomedicine are also highlighted. However, more studies and efforts have to be carried out for developing novel nano-therapeutics with high selectivity, sensitivity, biocompatibility, and minimal side effects in PDT.