•Overview of the transition metal complexes as photosensitizers.•Integration of metal complexes with biomolecules for targeted antitumor application.•The future perspectives for metal-based PSs are outlined. Light, oxygen and photosensitizers (PSs) are the three separate elements that have been applied in combination in the phototherapy of cancers in the past decades. Currently, platinum (Pt)-based drugs still account for approximately 50% of traditional chemotherapies used in the clinic. Transition metal complexes with unique and versatile photochemical and photophysical properties have appeared as promising systems for both photodynamic therapy and photoactivated chemotherapy. The highly potent photobiological activity based on energy transfer and electron transfer processes takes advantage of these properties. In this perspective article, we discuss the development of transition metal complexes (TMCs) with meaningful designs for the diagnosis and therapy of malignant tumors, including octahedral Ru(II) (ruthenium), Pt(IV) and Rh(III) (rhodium) PSs and in the early stages of Ir(III) (iridium) and Os(II) (osmium) complexes. The combination of organometallics with other active targeting moieties, such as antibodies, peptides, and aptamers, resulting in increased selectivity and reduced side-effects, will then be discussed. The challenges and future perspectives in this field will also be discussed. This review not only provides useful information for the future design of chemically innovative TMC-based anticancer drug candidates with clear mechanisms of action and drug targets, but also sheds light into the discovery of metal-based PSs to improve cancer treatment.