Structural and energetic transformations in the plasma membrane of a cancerous cell are investigated together with related consequences for the insertion of small cationic compounds. Molecular dynamics simulations are performed with an empirical force field on two membrane models that represent the membrane of a cancerous cell (M-Cancer) and of a healthy cell (M-Eukar), respectively. An eight-fold increase of negatively charged phosphatidylserine in the external membrane layer as well as a reduction of cholesterol concentration by half is taken into account to describe the membrane transformation. Three additional reference membranes are prepared and consist of pure phosphatidylcholine (M-PC), where 20% is replaced with phosphatidylserine (M-PC_0.8S_0.2), and where 34% is replaced with cholesterol (M-PC_0.66Ch_0.34), respectively. Moreover, the free energy released by inserting octadecylmethylimidazolium (OMIM⁺), a cation found in a class of common ionic liquids, into M-Eukar, M-Cancer as well as into the three reference model membranes is derived by applying thermodynamic integration. We find that the presence of serine improves the solvation of the membrane through favorable electrostatic interactions with solvated sodium ions, where a significant number of sodium ions are capable of penetrating the upper polar layer of the membrane. However, the insertion free energy of OMIM⁺ does not seem to be influenced by serine in the membrane. Furthermore, a significant serine induced structural reorganization of the membrane is not observed. In contrast, a reduction of cholesterol in the membrane models leads to smaller lipid surface densities, thinner membranes as well as less ordered and less stretched lipids as expected. We also observe that cholesterol reduction leads to a rougher membrane surface and an increased solvent accessibility of the hydrophobic membrane core. Membrane insertion of OMIM⁺ becomes significantly more favorable in the absence of cholesterol, with an increased insertion free energy release of 7.1 kJ mol⁻¹ in M-Cancer compared to M-Eukar. Overall, the results suggest only a minor influence of serine on membrane organization but do not rule out an influence on cation insertion through a stronger cation adsorption to the membrane surface. In contrast, cholesterol seems to impede OMIM⁺ insertion by increasing the density of polar lipids on the membrane surface and by flattening the membrane surface. These observations are shedding some light on the previously observed selective disruption of cancerous cells induced by cationic compounds such as found in ionic liquids.