Tentatively interested, but MC has the awareness of a brick. Also, I'mma need a diagram of this family tree.
1. It's his friend Itsuki's family guest house
2. Onee-san runs it with her parents
3. She is not related to Itsuki
So wtf is she to Itsuki? Step-sister? Aunt but not related by blood (i.e. was married to Itsuki's uncle, now widowed) ? She says 'Aunt' but I either don't trust her or don't know if she meant it literally or just as a generic 'Obasan'. It's only not weird for Itsuki to be playing wingman if she's his Step-Sister, but this being a Manga you'd expect him to try to get it himself.
The family situation becomes a little more clear in chap. 2 (it's a weekly so ch. 3 is coming out soon) but she doesn't say that she's not related to Itsuki. Just that they're not 親子, a real mother and son, even though she introduced herself as Itsuki's mom in the call to the MC's mom. Her last name being same as Itsuki's, she's probably his father's younger sister, younger because she uses 伯母 and not 叔母.
As for Itsuki's parents, they're probably dead. She says 両親いねぇの and in that context, that's usually an euphemism for dying. But with enough wiggle room to bring them back, if that suits the plot. Because it's used for something or somebody not just disappearing, but disappearing from where they should be.