Global fire activities, which are getting worse due to climate change, cause both environmental and human health hazards. Firefighters, being the first responders, are frequently exposed to heat which may impact their immune system and overall health. However, the nature of the impact of chronic heat exposure on immune function has not been studied in-depth in firefighters. In this study, 22 firefighters exposed to “heavy-smoke fires (structural fires)”, categorized as the “high-exposure group” (>0.15 structural fires/week) and “low-exposure group” (<0.15 structural fires/week), were sampled. Peripheral blood was examined for immune cell profile based on total and differential cell counts, immune function based on the transcriptional expression of drivers of innate and adaptive immunity and key inflammation mediators, and heat stress marker HSP70. The white blood cell (WBC) count, mean corpuscular volume, mean corpuscular hemoglobin, and absolute and segmented neutrophil counts decreased below the normal range in both exposure groups. The gene transcript levels for toll-like receptors (TLR2, TLR4, but not TLR7) and their adaptor protein MYD88 were lower whereas those for T-cell transcription factors (RORC/RORγ, FoxP3) and inflammatory mediators (TNF-α, Granzyme-B) were higher in the “high-exposure group”, indicating mixed response; however, the ratios between pro-inflammatory and anti-inflammatory transcription factors of adaptive immunity, namely T-bet/FoxP3 (Th1/Treg) and RORC/FoxP3 (Th17/Treg), were lower. Collectively, decreased immune cell landscape, downregulated key innate immunity receptors, and Tregs’ dominance suggested that chronic heat exposure in firefighters dysregulated innate and adaptive immunity, skewed towards an overall immunosuppressive condition with inflammation.