Laminate substrates in advanced IC packages serve as not only the principal heat dissipation pathway but also the critical component governing the thermomechanical performance of advanced packaging technologies. A solid and profound grasp of their thermomechanical properties is of crucial importance to better understand IC packages’ thermomechanical behavior. This study attempts to introduce a subregion homogenization modeling framework for effectively and efficiently modeling and characterizing the equivalent thermomechanical behavior of large-scale and high-density laminate substrates comprising the non-uniform distribution and non-unidirectional orientation of tiny metal traces. This framework incorporates subregion modeling, trace mapping and modeling, and finite element analysis (FEA)-based effective modeling. In addition, the laminates are macroscopically described as elastic orthotropic or elastic anisotropic material. This framework is first validated with simple uniaxial tensile and thermomechanical test simulations, and the calculation results associated with these two effective material models are compared with each other, as well as with those of two existing mixture models, and direct the detailed FEA. This framework is further tested on the prediction of the process-induced warpage of a flip chip chip-scale package, and the results are compared against the measurement data and the results of the whole-domain modeling-based effective approach and two existing mixture models.