This paper proposes a low-profile textile-modified meander line Inverted-F Antenna (IFA) with variable width and spacing meanders, for Industrial Scientific Medical (ISM) 2.4-GHz Wireless Body Area Networks (WBAN), optimized with a novel metaheuristic algorithm. Specifically, a metaheuristic known as Coral Reefs Optimization with Substrate Layer (CRO-SL) is used to obtain an optimal antenna for sensor systems, which allows covering properly and resiliently the 2.4–2.45-GHz industrial scientific medical bandwidth. Flexible pad foam has been used to make the designed prototype with a 1.1-mm thickness. We have used a version of the algorithm that is able to combine different searching operators within a single population of solutions. This approach is ideal to deal with hard optimization problems, such as the design of the proposed meander line IFA. During the optimization phase with the CRO-SL, the proposed antenna has been simulated using CST Microwave Studio software, linked to the CRO-SL by means of MATLAB implementation and Visual Basic Applications (VBA) code. We fully describe the antenna design process, the adaptation of the CRO-SL approach to this problem and several practical aspects of the optimization and details on the algorithm’s performance. To validate the simulation results, we have constructed and measured two prototypes of the antenna, designed with the proposed algorithm. Several practical aspects such as sensitivity during the antenna manufacturing or the agreement between the simulated and constructed antenna are also detailed in the paper.