Zinc oxide (ZnO) nanoparticles (NPs) are among the most actively investigated metal oxide nanomaterials, owing to their wide direct bandgap (3.37 eV), high exciton binding energy (60 meV), tunable morphology, and dose‐dependent biocompatibility. Although numerous reviews catalogue ZnO synthesis routes, a critical, parameter‐resolved comparison of conventional and green approaches, explicitly linked to application performance, remains scarce. This review addresses that gap by integrating, within a single framework: (i) a comparative analysis of physical, chemical, and biological synthesis routes; (ii) a parameter‐by‐parameter discussion (precursor, pH, temperature, calcination, phytochemical fingerprint) of how reaction variables govern crystallite size, defect chemistry, surface charge, and bandgap; (iii) structure–property–activity correlations linking morphology, oxygen‐vacancy density, and Zn 2 + ‐ release kinetics to photocatalytic, antimicrobial, anticancer, drug‐delivery, and agricultural performance; and (iv) a four‐pillar roadmap (reproducibility, scalability, regulation, and toxicity) toward industrially viable, regulation‐compliant ZnO NPs. Critical evaluation of recent studies shows that plant‐ and microbe‐mediated routes yield wurtzite ZnO NPs of 5–50 nm, achieving 80%–99% dye‐degradation and antimicrobial activity matching or exceeding chemical counterparts, provided batch reproducibility and dose‐controlled biosafety are addressed. Claims of “non‐toxicity” are qualified throughout by dose, particle size, and exposure conditions.