Muscles get tired when there is shortfall of ____.

Muscle fatigue or tiredness occurs primarily when there is a short supply or depletion of Adenosine Triphosphate (ATP) and glycogen reserves during sustained or intense contraction. ATP is the primary energy currency of the cell required for muscle contractions. When oxygen supply is limited, anaerobic respiration takes place, leading to a accumulation of lactic acid, but the shortfall causing the fatigue is that of energy molecules like ATP.