This perspective commemorates 50 years of surface-enhanced Raman scattering (SERS) by highlighting the paradigm shift toward rationally designed semiconductor substrates, enabling ultrasensitive and molecule-selective detection. Several enhancement strategies have been developed to effectively modulate the electronic band structure and charge transfer (CT) processes, such as energy level customization, amorphization, quasi-metallization, and morphology control, achieving high enhancement factors with good selectivity and stability. Moreover, semiconductor SERS substrates show broad prospects in the fields of bio-sensing and cancer diagnosis. Nevertheless, standardization gaps in substrate reproducibility and data comparability hinder its widespread adoption. Resolving these challenges through multi-stakeholder collaboration is essential to bridge the technology transfer gap and establish SERS as a core platform for next-generation inspection.