To gain insight into needle-free drug delivery based on micro-projectile penetration, a practical approach is to simulate the physical process in a controllable tissue simulant. SEBS (styrene-ethylene-butylene-styrene) mineral-oil gels are a promising simulant because their mechanical response can be systematically tuned by polymer concentration. In parallel to such surrogate-based experiments, analytical and numerical models are used to interpret and predict penetration. On the analytical side, penetration experiments have been rationalized using drag/resistance-type descriptions, such as modified Clift–Gauvin frameworks, from which concentration-dependent “apparent” viscosity and resistance can be inferred. On the numerical side, meshfree approaches such as SPH provide a natural way to capture large deformation and the penetration process. Here, an experimentally informed SPH framework for predicting penetration depth in SEBS gels is developed. Nonlinear elasticity and linear viscoelastic relaxation are parameterized using published tensile, compression, and small-strain rheology datasets for SEBS gels across multiple concentrations (e.g., 15–40 vol% SEBS). An Ogden hyperelastic model is employed, while time dependence is represented via a Prony-series relaxation spectrum consistent with frequency-dependent rheological response. Simulations are validated against experimental penetration measurements across gel concentrations, and sensitivity analyzes are performed to quantify how nonlinear elasticity, relaxation spectrum, and concentration jointly govern penetration depth. This approach strengthens experiment-to-simulation transfer by tying penetration predictions to measurable material behavior, enabling more mechanistic interpretation and more reliable extrapolation to new injection conditions and layered surrogate designs.