Host-directed therapy (HDT) has emerged as a promising strategy for managing infectious diseases by targeting host immune pathways rather than pathogens directly. However, the rational design of HDT approaches remains challenging due to the complexity of host–pathogen interactions, limitations in gene-editing delivery, and constraints in computational modeling. This review presents a conceptual framework integrating three advanced technological domains: quantum-inspired computation, CRISPR-Cas9 gene editing, and nanotechnology-based delivery systems. We propose a functional pipeline in which computational approaches, including quantum molecular simulation and machine learning, support the design of guide RNAs and optimization of nanoparticle formulations. These are coupled with CRISPR-based modulation of key host immune targets, particularly the NLRP3 inflammasome and IL-1 signaling pathways, followed by targeted delivery using lipid nanoparticles and nanoemulsion systems.The review synthesizes current knowledge across CRISPR biology, nanomedicine, immunology, and emerging quantum computational approaches, while critically addressing existing limitations, technological gaps, and translational challenges. We highlight key contradictions in the literature, identify priority research directions, and outline a structured roadmap for future investigation.Although the complete integration of these technologies remains aspirational, each component is individually supported by strong experimental evidence. This framework therefore represents a realistic and forward-looking strategy for advancing host-directed therapies in infectious diseases within a One Health context.