In summary, we developed an adipocyte-targeted nanocomplex, pTSL@(P+I), with synergistic pharmacological and photothermal effects for promoting white adipose tissue browning and combating obesity through upregulating UCP1 and COX5B expression by activating the transcription axis of PPARγ/PGC1α and HSF1/PGC1α. Here, COX5B is linked to obesity due to melanocortin 4 receptor deficiency.