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This study employed a dual\u2010acceptor engineering strategy utilizing isoindigo and selenium\u2010substituted [1,2,5]thiadiazolo[3,4\u2010<jats:italic>c<\/jats:italic>]pyridine to augment the molar extinction coefficient and spin\u2010orbit coupling effect, respectively, resulting in a substantial enhancement of photon\u2010absorption ability and non\u2010radiative decay energy\u2010release process of donor\u2010acceptor type phototherapy molecules. As the optimal phototherapy agent, IID\u2010PSe exhibited a high molar extinction coefficient two times that of photosensitizer, excellent <jats:sup>1<\/jats:sup>O<jats:sub>2<\/jats:sub> yield (15%) and PCE (34%), exhibiting great potential for phototherapy. After encapsulating with DSPE\u2010PEG2000, IID\u2010PSe NPs showed excellent anti\u2010tumor phototherapy ability both in vitro and in vivo. 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