AbstractUnderstanding the interaction between cells and nanoparticles (NPs) is vital to understand the hazard associated with nanoparticles. This requires quantifying and interpreting dose‐response relationships. Experiments with cells cultured in vitro and exposed to particle dispersions mainly rely on mathematical models that estimate the received nanoparticle dose. However, models need to consider that aqueous cell culture media wets the inner surface of hydrophilic open wells, which results in a curved liquid‐air interface called the meniscus. Here the impact of the meniscus on nanoparticle dosimetry is addressed in detail. Experiments and build an advanced mathematical model, to demonstrate that the presence of the meniscus may bring about systematic errors that must be considered to advance reproducibility and harmonization is presented. The script of the model is co‐published and can be adapted to any experimental setup. Finally, simple and practical solutions to this problem, such as covering the air–liquid interface with a permeable lid or soft rocking of the cell culture well plate is proposed.