Multi-energy calibration (MEC) and high matrix introduction (HMI) system were evaluated as strategies for direct analysis of simulated gastrointestinal chyme to estimate the in vitro bioaccessibility of essential elements and As in raw and cooked shrimp by inductively coupled plasma optical emission and mass spectrometry (ICP OES and ICP-MS). Based on the error propagation approach for multi-signal calibration methods, the limits of quantification (LOQs) of the MEC-ICP OES procedure ranged from 0.1 to 61 mg kg⁻¹ for Cu and S, respectively, while the LOQ for As quantification by HMI-ICP-MS was 0.1 mg kg⁻¹. The trueness was evaluated by a mass-balance study and comparing the results with those obtained through the microwave-assisted digestion reference procedure. Under optimized conditions, no significant differences were observed between the results obtained by the proposed direct analysis procedures and the reference method at the 95% confidence level; suitable mass balances within the 80–104% range were obtained. In vitro bioaccessibilities in cooked shrimp ranged from 14 to 78% for Zn and Ca, respectively. The heat treatment has increased the bioaccessibility for Cu and, to a lesser extent, for Fe, whereas a reducing trend was observed for Zn bioaccessibility. No influence of cooking on As bioaccessibility was found. The proposed procedures proved to be outstanding analytical strategies for elemental bioaccessibility studies, providing simplicity and high sample throughput compared to conventional approaches.