Integrated circuit (IC) packages employing a thermal conductive semiconductor package substrate with die region split and related fabrication methods are disclosed. The package substrate includes a die split where metal contacts in one or more dielectric layers of the package substrate underneath the IC die(s) are thicker (e.g., in a core die region) than other metal contacts (e.g., in a peripheral die region) in the dielectric layer. This facilitates higher thermal dissipation from the IC die(s) through the thicker metal contacts in the package substrate. Cross-talk shielding of the package substrate may not be sacrificed since thinner metal contacts of the package substrate that carry high speed signaling can be of lesser thickness than the thicker metal contacts that provide higher thermal dissipation. The dielectric layer in the package substrate may also include dielectric materials having different thermal conductivities to further facilitate thermal dissipation and/or desired electrical or mechanical characteristics.