This work proposes a mesostructure-guided computational framework to evaluate the effective thermal conductivity (ETC) of concrete affected by aggregate and interfacial transition zone (ITZ) configurations at a mesoscopic scale. An unified aggregate shape descriptor for gravels and crushed rocks is characterized by superellipsoid covering from convexity to non-convexity, as well as random static and dynamic packings of superellipsoidal aggregates (SAs) are carried out to generate tri-phase concrete mesostructures consisting of homogeneous mortar, densely packed aggregates and their surrounding ITZs. A closed-form expression for the ITZ volume fraction is theoretically developed in the present concrete mesostructure, which is also validated using the one-point probability function simulation. Moreover, an optimized Browanian motion numerical strategy is developed to estimate the ETC of tri-phase concrete. This strategy is confirmed to be an accurate numerical technique by comparing against the Mori-Tanaka model. The present framework reveals the quantitative responses of various configurations on the ETC, which manifest rigorous “constituent-mesostructure-ETC” relations. The results are available for tailoring components to optimize ITZ structures for the improvement of thermal efficiency and durability of buildings.