The recent surge of COVID-19 related to the Omicron variant emergence has thrown a harsh light upon epidemic control in the near future. This should lead the scientific and medical community to question the long-term vaccine strategy for SARS-CoV-2 control. We provide here a critical point of view regarding the virological evolution, epidemiological aspects, and immunological drivers for COVID-19 control, including a vaccination strategy. Overall, we need more innovations in vaccine development to reduce the COVID-19 burden long term. The most adequate answer might be better cooperation between universities, biotech and pharmaceutical companies