The Two-Higgs-Doublet-Standard Model-Axion-Seesaw-Higgs-Portal inflation (2hdSMASH) model consisting of two Higgs doublets, a Standard Model (SM) singlet complex scalar and three SM singlet right-handed neutrinos can embed axion dark matter, neutrino masses and address inflation. We report on an investigation of the inflationary aspects of 2hdSMASH and its subsequent impact on low energy phenomenology. In particular, we identify inflationary directions for which the parameter values required for successful inflation do not violate perturbative unitarity and boundedness-from-below conditions. By analyzing the renormalization-group flow of the parameters we identify the necessary and sufficient constraints for running all parameters perturbatively and maintaining stability from the electroweak to the PLANCK scale. We observe that stringent constraints arise on the singlet scalar self coupling from inflationary constraints, i.e., λS ∼ 10-10. Further, we find that all theoretical and experimental constraints are satisfied if the portal couplings are typically in the range (v/vS ) and (v/vS )2 (where v, vS refer to the electroweak and singlet scalar vacuum expectation value respectively). As a consequence, inflation is realized in a variety of field space directions in the effective single field regime. Finally we provide testable benchmark scenarios at colliders.