This paper is dedicated to high-order effects of thermal lagging in correlation with heat transfer models in micro- or nanoscale, relating the number of energy carriers and the associated resonance phenomenon under high-frequency excitations. Thus, a class of constitutive equations is considered for the heat flux describing high-order effects in the lagging behavior of heat transport. Tzou’s model, which is based on time-differential dual-phase-lag approximations of heat conduction, is generalized, incorporating the microstructural interaction effect in the fast-transient process of heat transport. More precisely, polynomial approximations of order n for the heat flux vector and of order m for the gradient of the temperature variation are considered. Further, well-posedness is established for solutions of the specific initial boundary value problems for the mathematical model when: (i) ; (ii) ; and (iii) . This means that uniqueness and continuous dependences of solutions are established with respect to the given prescribed data. With this aim, some modified initial boundary value problems related to the operators of the constitutive equation are introduced and suitable time-weighted measures of the solution are presented, and are used to establish the uniqueness theorems and to generate some estimates describing the continuous dependence of solutions with respect to the given data for each of the three cases specified. Moreover, the spatial behavior of the transient solutions is studied and an influence domain result is established for , while for some exponential decay estimates of Saint-Venant type are established. All results are established without restrictions on the characteristic parameters of the constitutive equation other than that the product of the coefficients of the time derivatives of greatest order of the two operators involved in the constitutive equation is positive.