Self-organized patterns of nematic liquid crystals (NLCs) are indispensable in sensing and opto-electronics due to their intricate molecular sensitivities. A molecular-scale investigation of solvated thin NLC films reveals that concurrent discontinuities in NLC–NLC interaction-driven thermodynamic properties, mobility, and rheological responses engender the incipient and necessary conditions for dewetting. This spontaneous dewetting is followed by self-organized morphological evolution, which proceeds through concentration-dependent distinct pathways. These discontinuities arise from an entropic landscape generated by a sufficient fraction of solvent molecules—an effect absent in pure thin NLC films, overcoming a long-standing challenge in achieving controlled self-organized patterns in such systems. The magnitude of these discontinuities governs film instability and the resulting morphological transitions with varying molecular orientations, consistent with the developed continuum-scale theory and previous experimental observations. This continuum framework, developed for the first time for solvated anisotropic systems, incorporates anisotropic contributions of NLC molecules derived from molecular-scale energetics and accurately recovers the characteristic pattern length scales in agreement with experiments. This enables the establishment of a multi-scale, unified framework, as deployed in this study, for solvent evaporation-induced nano/microfabrications.