Photonics has spurred a myriad of diagnostic and therapeutic applications for defeating cancer owing to its superiority in spatiotemporal maneuverability and minimal harm. The limits of light penetration depth and elusiveness of photosensitizer utilization, however, impede the implementation of the photodiagnostic and -therapy for determining and annihilating the deep-situated tumor. Herein, a promising strategy that harnesses functional optical fibers is developed and demonstrated to realize an in vivo endoscopic cancer sensing and therapy ensemble. Tumor detection is investigated using hypoxia-sensitive fluorescent fibers to realize fast and accurate tumor recognition and diagnosis. The tumor treatment is further performed by exploiting the endogenous photothermal effect of rare-earth-doped optical fibers. The eradication of orthotopic and subcutaneous xenografts significantly validates the availability of tumoricidal fibers. The strategy opens horizons to inspire the design of optical fiber-mediated "plug and play" precise tumor theranostics with high safety, which may intrigue broader fields, such as fiber optics, materials, chemistry, medicine, and clinics.© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.