Hypersensitivity pneumonitis (HP) and sarcoidosis are granulomatous interstitial lung diseases with overlapping clinical and immunological features, posing diagnostic and therapeutic challenges. This review offers a comprehensive assessment of their immune mechanisms, etiology, and pathogenesis. HP is predominantly triggered by exposure to environmental antigens, while sarcoidosis involves an exaggerated immune response to elusive antigens. Both diseases are driven by Th1 and Th17 pathways, regulatory T-cell dysfunction, and cytokine-mediated granuloma formation. Emerging diagnostic and prognostic biomarkers, such as KL-6, GDF15, PD-1, TIGIT, and genetic regulators including m6A and m5C modifications, provide valuable insights for disease stratification. Incorporating findings from a total of 38 studies (HP: n = 13
sarcoidosis: n = 25) published in the last 5 years, this review highlights key immune regulatory mechanisms, identifies critical research gaps, and provides directions for improving differential diagnosis. Addressing these gaps through multi-omics integration, computational tools, and interdisciplinary collaboration holds significant potential for refining diagnostic accuracy, advancing therapeutic strategies, and improving patient outcomes in both HP and sarcoidosis.