A report was received shortly before 9am that offenders had forced entry to the Honey Rose Foundation on Cotham Street sometime between 5pm on Wednesday and 8.40am today.
The offenders smashed a window to gain entry before making an untidy search and taking a quantity of donated cash and an empty till.
CCTV, witness and forensic enquiries are ongoing to establish the full circumstances and locate those responsible.
Community Inspector Matt Drennan said: "I am sure the wider community will share our disgust that someone has targeted a charity in this way.
"It is a despicable offence and I would like to reassure the community that we are working to identify the person or people responsible so that they can be brought to justice.
"I would appeal to anyone who was in the area overnight and noticed anything suspicious near to or outside the charity shop to contact police. Your information will be looked at thoroughly and could really help our enquiries.”
Anyone with information is asked to contact Merseyside Police social media desk via Twitter @MerPolCC or Facebook Merseyside Police CC. You can also call 101 quoting incident reference 18200214579 or contact the independent charity Crimestoppers anonymously, on 0800 555 111 or via their online form at: https://goo.gl/fzPgye. https://goo.gl/iEvHM9