Purpose <p>Drug resistance is a major challenge in the treatment of tumor diseases, especially in glioblastoma (GBM), where temozolomide (TMZ) plays a critical role. However, the development of resistance to TMZ occurs rapidly in more than half of the patients who initially respond to the drug. This highlights the need for novel approaches to overcome drug resistance and improve therapeutic outcomes in GBM treatment.</p> Methods <p>In our study, we combine TMZ treatment with wireless optoelectronics using advanced multilayered organic semiconductor (MOS) devices. These devices consist of a 200&#xa0;nm thick stack of metal and p–n semiconducting organic nanocrystals. When illuminated in physiological solutions, these MOS devices charge up and convert light pulses into localized displacement currents, which are strong enough to electrically stimulate tumor cells at safe light intensities. Importantly, the freestanding MOS devices require no external wiring or bias and remain stable under physiological conditions. The semiconductor layers are created from common, non-toxic pigments using simple, scalable deposition methods.</p> Results <p>Our results demonstrate that this combination of TMZ and optoelectronic stimulation significantly enhances apoptosis in tumor cells, thereby improving the effectiveness of TMZ in treating glioblastoma.</p> Conclusion <p>his research suggests that the integration of wireless optoelectronic stimulation with TMZ treatment offers a promising strategy to overcome drug resistance in GBM. The use of MOS devices enhances the therapeutic effect of TMZ and could lead to better treatment outcomes for patients with glioblastoma.</p> Graphical Abstract <p></p>