Methods and apparatus for analyzing fatigue of a structure and optimizing a characteristic of the structure based on the fatigue analysis are disclosed herein. An example method disclosed herein includes obtaining mass and unit stress values of a plurality of details of interest of a structural component, calculating fatigue margins for each of the details of interest, identifying among the calculated fatigue margins any negative fatigue margins associated with one or more of the details of interest, and adjusting, via a processor, a dimensional characteristic of each detail of interest associated with the negative fatigue margin(s) until positive fatigue margin(s) at each detail of interest is obtained.