SARS-CoV-2 continues to spread across the world as a highly transmissible endemic disease. For many cancer patients, SARS-CoV-2 infection is unavoidable. It continues to disrupt cancer care, causing treatment delays and major psycho-socio-medical issues. At present, there is limited evidence on safe prescribing of anti-cancer therapy, and safe treatment restart following SARS-CoV-2 infection. We conducted a prospective cohort study involving 406 COVID-19-positive cancer patients across five UK cancer centres and collected data on delay durations, COVID-19 symptoms and mortality, to ascertain the effect of treatment interruptions. Patients were studied between May 2022 and March 2023, during which Omicron variants of SARS-CoV-2 were predominant. Mean treatment interruption was 12.7 days (standard deviation 47.3 days). Upon resuming anti-cancer therapy, 8.5% experienced COVID-19 symptom progression, and 1.2% succumbed to COVID-19-related mortality. Patients with haematological cancers had a 3.4-fold increased risk of severe symptoms at 4 weeks compared to solid tumour patients. Higher symptom burden at COVID-19 diagnosis was associated with a 3.0-fold increase in symptom severity at 4 weeks following treatment restart. At 8 weeks following restart, 2.1% had increased morbidity or mortality. We highlight the ongoing impact of COVID-19 on patients and cancer care, and the risk of resuming cancer treatments in patients with symptomatic COVID-19. Although the risk of mortality is relatively low upon treatment resumption, personalised approaches assessing cancer diagnosis and SARS-CoV-2 status are crucial. Treatments are also stopped due to other infectious conditions and our results could be reviewed in the context of yearly influenza pandemics.