Next-generation multiple-input multiple-output (MIMO) systems, characterized by extremely large-scale arrays, holographic surfaces, three-dimensional architectures, and flexible antennas, are poised to deliver unprecedented data rates, spectral efficiency and stability. However, these advancements introduce significant challenges for physical layer signal processing, stemming from complex near-field propagation, continuous aperture modeling, sub-wavelength antenna coupling effects, and dynamic channel conditions. Conventional model-based and deep learning approaches often struggle with the immense computational complexity and model inaccuracies inherent in these new regimes. This article proposes a Fourier neural operator (FNO) as a powerful and promising tool to address these challenges. The FNO learns function-to-function mappings between infinite-dimensional function spaces, making them exceptionally well-suited for modeling complex physical systems governed by partial differential equations based on electromagnetic wave propagation. We first present the fundamental principles of FNO, demonstrating its mesh-free nature and function-to-function ability to efficiently capture global dependencies in the Fourier domain. Furthermore, we explore a range of applications of FNO in physical-layer signal processing for next-generation MIMO systems. Representative case studies on channel modeling and estimation for novel MIMO architectures demonstrate the superior performance of FNO compared to state-of-the-art methods. Finally, we discuss open challenges and outline future research directions, positioning FNO as a promising technology for enabling the enormous potential of next-generation MIMO systems.