The rise of nanotechnology has created an ever-increasing need to probe structures on the atomic scale, to which transmission electron microscopy has largely been the answer. Currently, the only way to efficiently thin arbitrary bulk samples into thin lamellae in preparation for this technique is to use a focused ion beam (FIB). Unfortunately, the established FIB thinning method is limited to producing samples of thickness above ∼20 nm. Using atomistic simulations alongside experiments, we show that this is due to effects from finite ion beam sharpness at low milling energies combined with atomic-scale effects at high energies which lead to shrinkage of the lamella. Specifically, we show that attaining thickness below 26 nm using a milling energy of 30 keV is fundamentally prevented by atomistic effects at the top edge of the lamella. Our results also explain the success of a recently proposed alternative FIB thinning method, which is free of the limitations of the conventional approach due to the absence of these physical processes