Photo-thermal therapy (PTT) is a promising therapeutic approach for specifically targeting cancer tumors with fewer side effects due to its spatial controlled nature. Noble metal nanoparticles or metal oxides generate local heat at nanoscale upon light or magnetic field, respectively. However, cellular response in tumors to such local thermal stimuli remains unclear. In this study, we visualize intercellular communication following local plasmonic PTT stimuli in a cancer tumor model, spheroids, using a FRET-based ERK activity sensor protein. By conducting rapid 3D scanning with multi-photon fluorescence microscopy, we successfully visualized the propagation of ERK activity after PTT stimuli. Stimuli applied by a single gold nanoparticle to a single cancer cell in the 3D cellular assembly induces ERK activation in the PTT-exposed cell, which then propagates to adjacent neighboring cells. The propagation was analyzed using an AI-based program, 3DeeCellTracker, developed by Dr. C. Wen. We found that the response of ERK activity to local thermal stimuli occurs much faster than spontaneous ERK activity, with the activation signal propagation over a few cellular layers within a few tens of minutes. Since the propagation of the cellular response is much slower than heat propagation, the observed signal propagation likely occurs via intercellular communication. We are currently investigating the role of intercellular communications in enhancing PTT efficiency.