<p>Bronchiectasis is a chronic airway disorder characterized by persistent inflammation and structural damage, driven by dynamic interactions among neutrophils, macrophages, and epithelial cells. While current therapies—such as airway clearance techniques, inhaled antibiotics, and macrolides—provide symptomatic and antimicrobial benefits, they remain largely reactive and fail to address the underlying inflammatory networks that sustain disease progression. This review focuses on the central role of the neutrophil–macrophage–epithelial cellular triad in bronchiectasis pathogenesis. We synthesize evidence detailing how these cells communicate via cytokines, proteases, and extracellular traps to perpetuate a self-amplifying cycle of infection, inflammation, and tissue remodeling. By moving beyond a pathogen-centric perspective, this review aims to establish a coherent framework for understanding immune–epithelial crosstalk as a driver of disease heterogeneity and treatment resistance. Ultimately, we highlight how decoding these cellular circuits may reveal novel therapeutic targets capable of disrupting disease chronicity and advancing precision management in bronchiectasis.</p>