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In theoretical chemistry, several distance-based, degree-based, and counting polynomial-related topological indices (TIs) are used to investigate the different chemical and structural properties of the molecular graphs. Furtula and Gutman redefined the F-index as the sum of cubes of degrees of the vertices of the molecular graphs to study the different properties of their structure-dependency. In this paper, we compute F-index of generalized sum graphs in terms of various TIs of their factor graphs, where generalized sum graphs are obtained by using four generalized subdivision-related operations and the strong product of graphs. We have analyzed our results through the numerical tables and the graphical presentations for the particular generalized sum graphs constructed with the help of path (alkane) graphs.