A shape and size optimization framework is developed to improve the structural performance of the stiffened shell using isogeometric analysis. To accurately model the stiffened shell, the Lagrange multiplier method is employed to establish the coupling relationship of isogeometric degenerated shell elements and isogeometric degenerated beam elements. Due to the advantages of the non-uniform rational B-spline (NURBS), the unit normal direction vectors of the shell can be defined analytically, which guarantees stiffeners perpendicular to the skin. Additionally, the stiffeners can be easily generated based on the mapping relationship of the parametric space and the physical space of the shell. Analytical sensitivity is derived in detail, and the gradient-based optimization method can be used to solve the minimum compliance optimization problem owing to the high order continuity of NURBS. Three numerical illustrative examples are presented to verify the effectiveness of the proposed framework for the shape and size optimization of stiffened shells, consisting of a cylindrical shell patch, a hyperbolic shell, and a complex engineering segment. It is worth noting that the proposed framework is especially suitable for optimization problems of the stiffened shell, eliminating the need of complex feature extraction.