In this contribution, we report an efficient approach to multiplex electrospray ionization (ESI) sources for applications in analytical and preparative mass spectrometry. This is achieved using up to four orthogonal injection inlets implemented on the opposite sides of an electrodynamic ion funnel interface. We demonstrate that both the total ion current transmitted through the mass spectrometer and the signal-to-noise ratio increase by 3.8-fold using four inlets compared to one inlet. The performance of the new multiplexing approach was examined using different classes of analytes covering a broad range of mass and ionic charge. A deposition rate of >10 μg of mass-selected ions per day may be achieved by using the multiplexed sources coupled to preparative mass spectrometry. The almost proportional increase in the ion current with the number of ESI inlets observed experimentally is confirmed using gas flow and ion trajectory simulations. The simulations demonstrate a pronounced effect of gas dynamics on the ion trajectories in the ion funnel, indicating that the efficiency of multiplexing strongly depends on gas velocity field. The study presented herein opens up exciting opportunities for the development of bright ion sources, which will advance both analytical and preparative mass spectrometry applications.