Trophic links between the epipelagic (top 200 m) and mesopelagic layers of the Indian Ocean from 2002 to 2016 were investigated by carbon and nitrogen stable isotope ratios of 2405 samples that encompass the base of trophic webs, and primary, secondary and tertiary consumers. The samples include particulate organic matter, gastropods, gelatinous organisms such as salps and pyrosomes, crustaceans, mesopelagic fishes, micronektonic and nektonic squids, tuna and swordfish. Stable δ13C and δ15N values were used to investigate trophic and resource partitioning between epipelagic vs mesopelagic (migrators and non-migrators), ecological groups (zooplanktivorous vs micronektivorous), and at seamounts and off-seamount locations. We also investigated how contrasting environmental conditions within two biogeographic provinces, the ISSG (Indian South Subtropical Gyre) and EAFR (East African Coastal Province), influenced stable isotope patterns. Our data suggest that broad-scale biogeographic differences and local environmental conditions significantly shape stable isotope values. In oligotrophic systems, epipelagic migrating and non epipelagic-migrating organisms rely on food webs where suspended particles are 15N-enriched and organic matter recycled/re-processed. We show that seamounts form strong isotopic topographic barriers (which we define as “isobiome”) that impact the trophic linkages/connections between epipelagic migrants and non-epipelagic migrants, and those with zooplanktivorous feeding strategies. This study reveals that the trophic and resource partitioning in the ocean is more complex than initially thought, when environmental variability, bathymetric gradients, and a wider range of samples are taken into account compared to earlier studies. We also showed that warmer oceans led to a reduction in productivity and potential shifts in food web trophic structure that remain to be investigated further. Finally, we discuss how important it is to unravel this complexity on a global scale given the vulnerability of epipelagic and mesopelagic communities due to anthropogenic pressures in the Anthropocene.