Yuan and colleagues demonstrate that inhaled biodegradable nanosilica activates an alveolar macrophage–NK axis, triggering an IL-12/15/18 triad that programs memory-like NK cells. This non-fibrotic, cell-free strategy suppresses melanoma growth, prevents postsurgical recurrence, and synergizes with anti-PD-1, establishing a robust framework for in vivo NK cell immunotherapy.