A fiber-optic drug delivery strategy for synergistic cancer photothermal-chemotherapy is introduced, combining photothermal therapy and chemotherapy through an optical fiber endoscopic probe. The fiber core carries photosensitizers, while the surface is coated with antitumor agents via a temperature-responsive hydrogel film. This enables localized hyperthermia and thermal-stimuli drug release to target tumors. Built-in fiber sensors, including a reflective Mach-Zehnder interferometer (MZI) and fiber Bragg grating (FBG), monitor drug release and temperature in real time, enhancing treatment safety. The strategy improves drug delivery efficiency by leveraging photothermal-mediated enhanced permeability and hydrogel-assisted high drug retention, enabling a "central-to-peripheral" drug penetration mechanism. The fiber-optic system offers precise drug delivery, accurate drug release control, high drug permeability and retention in tumors, low off-target effects, and real-time drug release and temperature feedback, providing a straightforward and effective photothermal-chemotherapy pathway. The strategy holds promise for a revolutionary on-demand drug delivery platform for efficient antitumor drug evaluation and screening. The system was tested in vitro and in vivo, showing effective tumor eradication with minimal side effects. The fiber probe demonstrated high drug targeting efficiency, with no damage to normal tissues. The strategy's advantages include high drug delivery efficiency, minimal invasiveness, and versatility, making it suitable for various drug delivery applications. The fiber-optic drug delivery system is compatible with interventional therapy and can be used for different drugs, including fluorescent agents. The strategy offers a high-performance synergistic therapy for cancer treatment, with potential for future development in clinical applications.A fiber-optic drug delivery strategy for synergistic cancer photothermal-chemotherapy is introduced, combining photothermal therapy and chemotherapy through an optical fiber endoscopic probe. The fiber core carries photosensitizers, while the surface is coated with antitumor agents via a temperature-responsive hydrogel film. This enables localized hyperthermia and thermal-stimuli drug release to target tumors. Built-in fiber sensors, including a reflective Mach-Zehnder interferometer (MZI) and fiber Bragg grating (FBG), monitor drug release and temperature in real time, enhancing treatment safety. The strategy improves drug delivery efficiency by leveraging photothermal-mediated enhanced permeability and hydrogel-assisted high drug retention, enabling a "central-to-peripheral" drug penetration mechanism. The fiber-optic system offers precise drug delivery, accurate drug release control, high drug permeability and retention in tumors, low off-target effects, and real-time drug release and temperature feedback, providing a straightforward and effective photothermal-chemotherapy pathway. The strategy holds promise for a revolutionary on-demand drug delivery platform for efficient antitumor drug evaluation and screening. The system was tested in vitro and in vivo, showing effective tumor eradication with minimal side effects. The fiber probe demonstrated high drug targeting efficiency, with no damage to normal tissues. The strategy's advantages include high drug delivery efficiency, minimal invasiveness, and versatility, making it suitable for various drug delivery applications. The fiber-optic drug delivery system is compatible with interventional therapy and can be used for different drugs, including fluorescent agents. The strategy offers a high-performance synergistic therapy for cancer treatment, with potential for future development in clinical applications.