Recent developments in MEMS technologies have made such devices attractive for use in applications that involve precision engineering and scalability. In the biomedical industry, MEMS devices have gained popularity in recent years for use as single-cell manipulation and characterisation tools. A niche application is the mechanical characterisation of single human red blood cells, which may exhibit certain pathological conditions that impart biomarkers of quantifiable magnitude that are potentially detectable via MEMS devices. Such applications come with stringent thermal and structural specifications wherein the potential device candidates must be able to function with no exceptions. This work presents a state-of-the-art numerical modelling methodology that is capable of accurately predicting MEMS device performance in various media, including aqueous ones. The method is strongly coupled in nature, whereby thermal as well as structural degrees of freedom are transferred to and from finite element and finite volume solvers at every iteration. This method therefore provides MEMS design engineers with a reliable tool that can be used in design and development stages and helps to avoid total reliability on experimental testing. The proposed numerical model is validated via a series of physical experiments. Four MEMS electrothermal actuators with cascaded V-shaped drivers are presented. With the use of the newly proposed numerical model as well as the experimental testing, the MEMS devices’ suitability for biomedical applications is confirmed.