Systematic understanding of the impact of nanomaterials (NMs) on the health and activity of plant-associated microorganisms is required for sustainable development of efficient nano-enabled agrochemicals. Zinc (Zn) is an essential micronutrient for plant growth and development. It plays a vital role in various physiological processes, including enzyme activation, protein synthesis, cell division, etc. The present study investigated the effects of foliar exposure to different sizes of ZnO particles, including ZnO quantum dots (ZnO QDs, 4.06 nm), ZnO nanoparticles (ZnO NPs, 60.0 nm), bulk-scale ZnO particles (ZnO BPs, 464.5 nm), and Zn ions at an equivalent Zn molar concentration (0.61 mM) on the endophytic and rhizosphere microbial communities of pumpkin seedlings. ZnO QDs increased the total plant biomass by 24.6% as compared to the control. ZnO QDs also increased the contents of total chlorophyll and carotenoids, elevated micronutrient (Zn, Fe, and B) uptake, and triggered the activities of antioxidant enzymes, such as peroxidase (POD), polyphenol oxidase (PPO), and catalase (CAT), as compared to controls. The composition and diversity of the endophytic and rhizosphere bacterial or fungal communities were significantly altered as a function of ZnO NM size, and a significant difference between the control and ZnO treatments was also evident. Linear discriminant effect size analysis (LEfSe) shows that the putative beneficial host microbes Steroidobacter (relative abundance, RA: 1.05%) and Paenibacillus (RA: 0.59%) were enriched in pumpkin seedlings treated with ZnO QDs, which may lead to greater plant growth, nutrient acquisition, and stress resistance. Cooccurrence networks indicate that ZnO QDs increased both node and link numbers of the bacterial networks by 46.94 and 123.38% in the roots, which could further stabilize the microbial community and confer resistance to environmental disturbance. Our overall findings demonstrate that ZnO QDs could enhance plant growth both directly by improving physiological performances and indirectly by modulating beneficial endophytic and rhizosphere microorganisms. Thus, nano-enabled strategies can be a promising and sustainable approach to increase crop growth and resistance to stress.