The tropical Indian and Pacific Oceans play a crucial role for global climate due to their extensive coverage across the low latitudes. However, our understanding of the regional sea surface temperature (SST) dynamics during major interglacial periods - when Earth’s climate was warmer than the preindustrial period - remains limited. Here, we compare proxy-based SST reconstructions from the low-latitude Indo-Pacific with Community Earth System Model (CESM) simulations for three key interglacial intervals: the mid-Holocene, Marine Isotope Stage (MIS) 5e, and MIS 11c. Proxy data show an overall warming during MIS 5e and MIS 11c relative to the preindustrial period. Moreover, smaller zonal SST gradients across the equatorial Pacific indicate a weakening of the Pacific Walker circulation. We attribute these findings primarily to extratropical warming and its influence on ocean circulation, particularly the Atlantic Meridional Overturning Circulation and shallow meridional overturning circulation cells. In contrast, CESM simulations indicate lower-than-preindustrial SSTs during MIS 5e and MIS 11c peaks and a larger zonal gradient. We perform individual forcing experiments to disentangle the roles of orbital forcing, greenhouse gas concentration and vegetation cover in shaping SST anomalies. We find that the implementation of paleo-vegetation in CESM reduces the discrepancies between proxy and model data. However, it does not improve the zonal SST gradients, suggesting that model representations of tropical ocean and climate dynamics remain insufficient. Possible causes for these shortcomings are discussed. Our findings underscore the need for refined model physics and improved paleo-proxy integration to better simulate tropical climate behavior during interglacials.