It seems like it will happen at some point due to either a mass epidemic, cataclysmic natural disaster or potentially some brilliant but evil madman or government pulling off a mass self-destructing act.
One interesting thing to ponder is will humanity each other galaxies or planets once it happens or in the off chance, will we live on in some form forever?
/Sucks on thumb
One or catastrophic events [for example giant space rock followed by seismic upheaval] at which juncture a world already weakened by climate change and human-driven extinction goes down like dominoes.
I hear that the sixth great extinction event may already be underway. so...collapse of ecological systems, escalating conflict over resources we are burning through ever faster, widespread regional wars and collapse of governments if not an outright global war. Ensuing population crash accompanied by various diseases. Let's not forget that the end might only be one asteroid strike away. How would another incidence of solar activity on the scale of The Carrington Event [or worse] affect much of the technology we depend on.
Maybe scattered communities of humans might survive, but it could be as though we had abruptly been knocked back thousands of years. I hope some form of life can pull through and recover from this mess. In the long term, this planet is toast.
Humans will be lucky to establish a viable settlement on Mars. The only human artefacts with a chance of getting close to another star system will be whatever remains of the probes we have sent out. [See Douglas Adams on the size of the universe we live in.] Our television and radio broadcasts will already have rippled into the local cluster of star systems. These may well be distorted/drowned out by whatever they pass through and as the universe continues to expand.
In the cosmic blink of an eye, there will be nothing left to show that we existed.
As it has been for many hundreds of billions of life forms before us, our worlds will end when we lose consciousness for the last time.
[writing stuff is hard stuff, and I'm already wondering whether I should have speculated]