Chemotherapy represents a conventional method for cancer treatment, but it inevitably has the issues of low clinical efficacy, therapy resistance and severe side effect. In view of the unique characteristic of nanosystems that can deliver drugs in an effective and safe manner, we report a photoactivatable nano-liposome containing a hypoxia responsive prodrug tirapazamine (TPZ), glucose oxidase (GOx) and indocyanine green (ICG) for photothermal-triggered chemotherapy of subcutaneous metastatic breast cancer. The nano-liposomes (termed as IGT@NPs) are fabricated using a thermal-responsive liposome component to enable photoactivatable drug delivery via a photothermal effect. IGT@NPs mediate the local temperature increase under near-infrared (NIR) laser irradiation, not only allowing for photothermal therapy (PTT), but also achieving on-demand TPZ and GOx releases. In the tumor microenvironment, GOx catalyzes the consumption of glucose and oxygen, resulting in aggravated hypoxia level. As a consequence, TPZ is activated by the aggravated hypoxic microenvironment to trigger the chemotherapeutic action. Therefore, a photothermal-triggered chemotherapy is achieved by IGT@NPs, which leads to the effective inhibitions of primary tumor growth and metastatic tumor occurrence in subcutaneous 4T1 tumor tumors. This current study thus provides a photoactivatable nanosystem containing tripartite therapeutics for cancer treatment with controllable and combinational functions.