Air raids come as Palestinians in Rafah brace for offensive that aid agencies fear will cause massive casualties.
There were conflicting reports of the death toll following the pre-dawn strikes on Monday.
The AFP news agency reported that the strikes killed 52 people, while Reuters reported that 37 had been killed. Both outlets cited health officials in Gaza.
The Israeli strikes hit 14 houses and three mosques in Rafah, according to Palestinian officials.
Israel’s military said it had struck a number of “terror targets” in the Shaboura district of Rafah and the strikes had concluded.
Israel’s military also said it had rescued two captives taken by Hamas in an overnight operation in Rafah.
Military officials said the captives, named as Fernando Simon Marman and Louis Har, were in good condition.
Hamas has warned that an Israeli ground assault in Rafah would “blow up” negotiations to release the group’s remaining captives in Gaza.
The strikes on Rafah come as Israel is preparing to launch a major offensive that aid agencies fear will result in massive civilian casualties in the last relatively safe area of Gaza.
About 1.4 million Palestinians, or more than half the population of Gaza, have crowded into Rafah to escape Israeli bombardment, which has reduced much of the rest of the enclave to ruins.
United States President Joe Biden on Sunday warned Israeli Prime Minister Benjamin Netanyahu not to launch an offensive on Rafah without a “credible and executable plan” to ensure the safety of people sheltering in the city.
Netanyahu has promised “safe passage” for Palestinians in Rafah, but the lack of clarity about evacuation plans has prompted fears that they may be pushed into Egypt’s Sinai Peninsula, stoking tensions with Cairo.
Netanyahu on Sunday told Fox News that “there’s plenty of room” north of Rafah and that is “where we’re going to direct them”, without specifying which part of Gaza would be safe to evacuate to.