The utilization of refractive index (RI) change due to guest–host interactions between the guest volatile organic compound vapor and porous metal–organic frameworks (vapor–MOF interactions) is promising in photonic vapor sensors. Therefore, the study of light–matter interactions in nanoporous metal–organic frameworks (MOFs) is fundamental and essential for MOF-based photonic devices. In this work, the manipulation of light in MOFs to investigate the vapor–MOF interactions by using optical fiber devices is demonstrated. The vapor–MOF interactions and the light–vapor interactions (light in MOFs to sense the RI changes resulting from the vapor–MOF interactions) are investigated. The cladding mode is excited by a long-period fiber grating (LPFG) for evanescent field sensing in a ZIF-8 sensitive coating. The experimental results combining quantum chemical calculations and optical simulations reveal the relationships between the microscopic energy of vapor desorption, RI changes and evanescent field enhancement in ZIF-8 during the vapor–MOF interactions. With exceptionally large RI changes, the evanescent field of cladding mode in ZIF-8 is greatly enhanced to sense the vapor–MOF interactions. As a proof-of-concept, a LPFG sensor with ZIF-8 coating showed a high sensitivity of 1.33 pm ppm−1 in the linear range from 9.8 ppm to 540 ppm for the sensing of ethanol vapor. The investigation of light–matter interactions in ZIF-8 provides a useful guideline for the design and fabrication of MOF-based optical waveguide/fiber sensors.