Binding audiovisual content into multimedia applications requires the specification of each media item, including its size and position, to define a screen layout. The multimedia application author must plan the application’s screen layout (ASL), considering a variety of screen sizes where the application shall be executed. An ASL that maximizes the area occupied by media items on the screen is essential, given that screen space is a valuable asset for media broadcasters. In this paper, we introduce the Application Screen Layout Optimization Problem, and present its NP-hardness. Besides, two integer programming formulations and an Iterated Local Search (ILS) metaheuristic are proposed to solve it. The efficiency of the proposed methods is evaluated, showing that the metaheuristic achieves better results and is at least 12 times faster, on average, than the mathematical formulations. Also, the proposed approaches were compared to a layout design algorithm, showing their effectiveness.