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(1) Background: Nanoplastics are emerging environmental pollutants with potential toxic effects on aquatic organisms. This study investigates the toxicity of NPs in Biomphalaria glabrata, a freshwater snail species widely used as a bioindicator species in ecotoxicology studies.; (2) Methods: We exposed three generations (F0–F2) of B. glabrata snail embryos to different sizes of polystyrene nanoparticles and assessed responses.; (3) Results: We observed severe effects on F0 to F2 B. glabrata embryos, including size-dependent (30 to 500 nm) increases in mortality rates, size and dosage-dependent (1 to 100 ppm) effects on hatching rates with concentration-dependent toxicity in the 30 nm exposure group. The F2 generation embryos appear to be most responsive to detoxification (CYP450) and pollutant metabolism (HSP70) at 48-h-post-treatment (HPT), while our developmental marker (MATN1) was highly upregulated at 96-HPT. We also report a particle-size-dependent correlation in HSP70 and CYP450 mRNA expression, as well as enhanced upregulation in the offspring of exposed snails. We also observed significant reductions in hatching rates for F2.; (4) Conclusions: These findings indicate that F2 generation embryos appear to exhibit increased stress from toxic substances inherited from their parents and grandparents (F1 and F0). This study provides valuable insights into the impact of plastic particulate pollution on multiple generations and highlights the importance of monitoring and mitigating plastic waste.