McBurnie has been sidelined since breaking a bone in his foot during Sheffield United's Premier League match with Arsenal on April 11.
Now, just days before Scotland are set to finalise their quad, the 24-year-old announced he would not be involved in Euro 2020, delayed from last year as a result of the coronavirus pandemic.
"I'm devastated that I suffered a fractured metatarsal which ruled me out for the rest of the season and has unfortunately ruled me out for the euros," McBurnie wrote on Twitter.
"Not to be able to go to that tournament with the boys is heartbreaking for me. Thank you for all your messages and support."
Although McBurnie has not scored in 16 international appearances, he was successful during the the in a play-off final victory over Serbia that saw Scotland qualify for the Euros.
McBurnie has had his off-field problems as well of late, with Sheffield United launching an investigation after a video was circulated on social media that appeared to show him taking part in a street altercation.
A 24-year-old man was subsequently arrested and released on police bail pending further enquiries.
Scotland were already without inured midfielders Ryan Jack and Kenny McLean for the Euros, with their opening match against the Czech Republic on June 14.