This study aimed to investigate the in vitro lipolysis of five different self-nanoemulsifying drug delivery system (SNEDDS) formulations and to test the formulations by combining the in vitro lipolysis with ex vivo permeability and in situ perfusion methods as permeation steps, and then to compare the methods. Exemestane (EXE) was selected as the model drug due to its low solubility and nonionic nature. Four SNEDDS formulations, differing from the main formulation (MCFK40) in terms of cosolvent content (MCFCoS), oil type (LCF), digestible surfactant content (MCFT80), and oil amount (MCFI988), were prepared to contain equal EXE amounts and characterized. Firstly, a classical (without permeation step) in vitro lipolysis study was conducted for SNEDDS formulations and reference product. During lipolysis, higher drug precipitation, in other words, free drug fraction, was observed in formulations containing digestible excipients (MCFT80 and MCFI988) and reference. Subsequently, a sequential lipolysis - ex vivo permeability study was conducted for SNEDDS formulations and reference using a vertical Franz diffusion cell with porcine intestinal tissue with samples taken from lipolysis medium at different times (0., 15., and 60. min). The similar permeated EXE% and the area under the permeated EXE% - time curve values were obtained for all SNEDDS regardless of the free drug fraction. The different stages of SNEDDS lipolysis did not affect EXE permeability. Subsequently, the lipolysis study was coupled with an in situ perfusion study that would allow simultaneous lipolysis and permeation. MCFK40 and MCFI988, which were selected due to their differences in lipolysis extent and free drug fraction, and EXE solution were examined with this method. Despite the in vitro formulation differences, the two SNEDDS formulations showed similar effective permeability coefficient (Peff) values to each other and those of the EXE solution. It was shown that EXE's bioavailability problem due to low solubility could be overcome with SNEDDS formulations. Furthermore, the sequential lipolysis - ex vivo permeability study was found to capture the results of the simultaneous lipolysis - in situ perfusion study, which more closely simulates in vivo. This was attributed to the use of intestinal tissue as a permeation barrier, which allowed the diffusion of colloidal-sized micelles, vesicles, and lipid digestion products in the ex vivo study. Since the in situ perfusion method is not suitable for screening of lipid-based formulations (LBF), the first data for using in vitro lipolysis combined with Franz diffusion cell with intestinal tissue instead were presented in this study. Combining lipolysis with the permeation step is necessary for the evaluation of LBF. Although both methods used in this study are promising, further evaluations are needed regarding horizontal/vertical cells, surface/volume ratio, sequential/simultaneous evaluation, and comparison with pharmacokinetic data.