High-priced medicines such as patented innovators and oncology items are great burden to healthcare budgets and barriers to treatment access worldwide. This study investigates availability, medicine price and affordability of selected oncology and on-patent medicines (medicines that still have patent protection) in Malaysia’s public and private sectors. This cross sectional study adapted the validated methodology developed by the World Health Organization/Health Action International. Procurement and patient prices were collected from public and private facilities nationwide for a case study of four oncology and four on-patent medicines. Availability was reported as the percentage of medicine outlets with the medicine. For international comparison, median prices were compared against International Reference Price (IRP). Mark-up was calculated as the percentage of patient price to procurement price. Affordability was determined by the number of days’ wages required for selected treatment courses. The average availability of the selected basket of oncology and on-patent medicines were 53.9% and 51.0%, respectively. There were wide variations between public and private procurement prices of the medicines studied. Compared to international benchmarks, oncology drugs were procured at 0.2 to 3.2 times the IRP. Median retail mark-ups of originator and generic oncology medicines were 20.7% and 130.2%, respectively. High mark-ups of 41.4% were observed for on-patent medicines. Although generics were affordable, originators were unaffordable. To illustrate, low-income patients need to work for about three days to afford on-patent medicines and up to a year to afford one course of cancer treatment. Since there are no generic alternatives, patients that are not able to afford the needed treatment may not have other treatment alternatives. Sustainable financing for expensive medicines is needed to safeguard medicines access and prevent catastrophic outcomes. Policies to reward innovation should be balanced with affordability, as people from different socio-economic groups deserve the same treatment.