Pattern recognition receptors (PRRs) are fundamental to the innate immune system, functioning to detect and eliminate invading pathogens by inhibiting their replication and limiting host tissue damage. Through direct recognition of pathogen-associated molecular patterns and damage-associated molecular patterns, PRRs initiate inflammatory responses, including cytokine production, and modulate the adaptive immune response. Ligand binding activates downstream signaling pathways that promote pathogen clearance and drive inflammasome assembly. Accumulating evidence underscores the critical role of PRRs in sensing cellular damage and preserving homeostasis. Importantly, interactions within PRR networks facilitate the formation of multiple PRR-containing inflammasomes (PANoptosome), enabling coordinated inflammatory cell death under combined pathogen-associated molecular pattern and damage-associated molecular pattern stimulation. A comprehensive understanding of these interconnected signaling networks is essential for elucidating the regulation of innate immunity and its implications for disease pathogenesis, particularly in the context of infection and inflammation. This review provides a detailed overview of PRR-ligand recognition, downstream signaling mechanisms, and inflammasome activation, and discusses emerging insights into PRR regulation that hold promise for novel immunotherapeutic interventions.