Computed-aided molecular modeling methods are presented to estimate the melt transition temperatures, Tm′s, of polymers in solution and in the crystalline state. The molecular geometries and energetics are computed using fixed valence geometry molecular mechanics with the charge densities computed for monomers using the CNDO/2 semiempirical molecular orbital method. A calibration-based melt transition model can be used on a congeneric series of polymers where at least one known Tmis available to scale the computation. This model is applied to a set of collagen triple-helix tripeptide and hexapeptide analogs, and to four classes of crystalline synthetic polymers. The estimated Tm′s are in good agreement with the reported experimental values. Moreover, the trends to increase or decrease Tmas a function of change in chemical structure of the polymer are correctly predicted by the model. A first-principle phase transition formalism to predict the thermodynamic properties of polymer crystal melting is also presented. This model is based upon Ising-mean-field theory. Application of this formalism to polymethylene and polytetrafluoroethylene yields accurate predictions of Tmand the entropy of melting. However, the formalism is quite computationally intense and not meant for routine applications.