The widespread use of single-use plastic (SUP) water bottles has raised growing concerns about chronic human exposure to nanoplastics (NPs). This study presents a quantitative assessment of NP accumulation in human tissues resulting from the long-term consumption of SUP water bottles. Using survey-derived consumption data and the Human Exposure and Absorption Simulation Interface (HEASI) Plastic Model, we modeled NP intake, gastrointestinal (GI) retention, and whole-body tissue accumulation under steady-state conditions. Three exposure scenarios were developed based on published NP concentration data in SUP water bottles, ranging from 1.10 × 10⁵ to 1.0 × 10¹¹ particles/liter. Our findings reveal that whole-body tissue accumulation of NPs varies significantly with consumption habits and assumed biliary excretion rates, with modeled concentrations ranging from 0.00084 to 226.68 µg/L. These values represent the steady-state amount of nanoplastics absorbed into systemic circulation and retained in tissues, rather than simply the intake rate. The conversion to µg/L was based on the average mass per particle and reflects internal exposure levels relevant to toxicological assessment. The study also estimates NP concentrations in the GI tract and stool, highlighting substantial variability across exposure scenarios. Log10 analysis of NP concentrations indicates a dose-dependent accumulation trend, particularly under high-consumption and high-exposure scenarios, although some variability is observed in lower exposure brackets due to the dynamics of the kinetic model. Polyamide and polystyrene were modeled as the most prevalent NP types in tissues, based on their relative abundance in SUP water bottles; however, this extrapolation assumes uniform uptake and retention across polymers and should be interpreted with caution. These results suggest that chronic exposure to NPs from SUP water bottles may pose potential health risks, especially in populations with high consumption rates. This study calls for the development of regulatory benchmarks, improved detection methods, and reduced use of SUP water bottles to limit NP exposure and protect public health.