Structural integrity assessment of aging flight vehicles is extremely important to ensure their economic and safe operation. A two-step analytical approach, developed to estimate the residual strength of pressurized fuselage stiffened shell panels with multi-bay fatigue cracking is presented in this article. Conventional finite element analysis of the damaged multibay panel is first carried out to obtain the load flow pattern through it. The Schwartz-Neumann alternating method is then applied to the fuselage skin with mutiple site damage, to obtain stresses and the relevant crack tip parameters that govern the onset of fracture. Fracture mechanics as well as net section yield criteria are used to evaluate the static residual strength. The presence of holes with or without multisite damage ahead of a dominant crack is found to significantly degrade the capacity of the fuselage shell panels to sustain static internal pressure. An elastic-plastic alternating method is newly developed and applied to evaluate the residual strength of flat panels with multiple cracks. The computational methodologies presented herein are marked improvements to the present state-of-the-art, and are extremely efficient, both from engineering manpower as well as computational costs point of view. Once verified, they can very well complement the experimental requirements, reducing the cost of structural integrity assessment programs.