The single-mode approximation of the resonant state expansion has proven to give accurate first-order approximations of resonance shifts and linewidth changes when modifying the material properties inside open optical resonators. Here, we extend this first-order perturbation theory to modifications of the material properties in the surrounding medium. As a side product of our derivations, we retrieve the already known analytical normalization condition for resonant states. We apply our theory to two example systems: A metallic nanosphere and a one-dimensional photonic crystal slab.Nanophotonic structures such as photonic crystals or plasmonic nanoparticles compromise optical resonances with strong electromagnetic near-fields. Consequently, even tiny changes in the the surrounding materials can have significant influence on the resonances frequencies. This is the key to various kinds of optical sensing applications [1-7]. Fig. 1 displays exemplarily a metallic sphere, around which the surrounding permittivity is changed from ε to ε + ∆ε, thus shifting the resonance wavenumber from k m to k ν .The modeling of such systems often relies on extensive numerical simulations, which can be rather inefficient, since in many practical cases, the variations in the material properties are extremely small. In contrast, perturbative theories are particularly suited for these cases. They are based on the eigenmodes of the system, also known as resonant states (RS) or quasi-normal modes [8][9][10][11], and have proven to be very efficient for all kinds of perturbations inside or in close proximity to nanophotonic resonators [8,[12][13][14][15][16][17]. However, a general rigorous way to incorporate perturbations of the surrounding medium into the theory is missing so far. The main difficulty arises from the fact that nanophotonic systems exhibit RS that radiate to the far field, so that their field distributions grow with distance to the resonator [15,16,18]. Hence, conventional perturbative formulations for bound states, e.g., known from quantum mechanics, cannot be applied. Several normalization schemes have been developed in recent years (for details, see Refs. [9,10,19] and references therein), but no theory exists so far for perturbations in the exterior. In this Letter, we derive such a theory for homogeneous and isotropic perturbations.The frequency representation of Maxwell's equations [Gaussian units, time dependence exp(−iωt)] can be written as [19]