In vitro, SLC16A14 silencing suppressed tumor cell proliferation, invasion, and migration, supporting its role as a key molecule connecting stress adaptation and tumor progression.<h4>Conclusion</h4>We established an organelle stress program-based subtyping and prognostic framework for LUAD, revealed the coupling between stress adaptation and TME remodeling, and proposed SLC16A14 and its associated communication network as potential intervention targets, providing multiomics evidence for interpreting LUAD heterogeneity and for stratifying immunotherapy and combination strategies. Here, SLC16A14 is linked to neoplasm.