Concomitantly pursuing superior maize (Zeamays L.) productivity with grain quality is essential for food security. Therefore, this study provides a meta-analysis of 21 studies assembled from the scientific literature to tackle the effect of the two most limiting factors for maize production, water and nitrogen (N), and their impacts on grain quality composition, herein focused on protein, oil, and starch concentrations. Water stress levels resulted in erratic responses both in direction and magnitude on all the grain quality components, plausibly linked to a different duration, timing, and intensity of water stress treatments. Nitrogen fertilization more consistently affected the grain protein concentration, with a larger effect size for protein as fertilizer N levels increased (protein change of +14% for low, ≤70 kg N ha−1; +21% for medium, >70–150 kg N ha−1; and +24% for high, >150 kg N ha−1). Both starch and oil grain concentrations presented less variation to fertilizer N levels. The positive protein–oil correlation (r = 0.49) permitted to infer that although the oil concentration may reach a plateau (8%), further increases in protein are still possible. Augmented research on grain quality is warranted to sustain food production but with both high nutritional and energetic value for the global demand.