The pyramids of Cairo and the Coliseum of Rome remain part of inhabited metropolitan areas to this day, but certainly there are other large structures and extensive inhabited areas that were abandoned and "lost".

The closest I can give to a single answer is that human civilizations are not stable over periods of millennia, and a place that was once considered a major center of the world can become a backwater or a ruin in less time than you might think. Very few societies manage to keep the kind of long-lived continuity that ancient Rome or ancient Egypt used to (mostly justifiably) claim. For other major societies, which often seem to their citizens to be permanent fixtures of the world, the end can come sooner than you think, especially when you zoom out to a historical time scale. For example, every corner of the world in the late twentieth century was heavily influenced by the two superpowers. But the Soviet Union had arisen mere decades earlier from an unimportant backwater on the fringes of Europe, and would end up splintering after surviving barely over 70 years. The United States, in the meantime, had only been founded ~200 years earlier, and famous cities like Chicago and Los Angeles had grown to global importance over the course of a human lifespan. These are not long time spans from an archaeologist's perspective. And the volatile twentieth century may be an outlier, but it's not a complete exception: the Incan empire was enormous and incredible for its time, and it lasted (if I remember correctly) something like 90 years before the conquistadors destroyed it.

So what about specific causes, if we can try and generalize to a few points? Wars and political events shift the center of power in a region, if not raze cities and drive out the inhabitants outright. Natural events (disease, volcanic eruption, earthquake) can suddenly make a place dangerous to inhabit, or weaken it enough to give its rivals an opportunity to grow in influence. Trade routes can rise or fall in importance due to economic or technological shifts, or because of other changes happening around distant trading partners.

Less predictable effects can stem from cultural shifts as well. When power is concentrated, idiosyncracies of rulership can create sudden changes: for example, the pharoah Amenhotep IV attempted to replace all of Egypt's religion with monotheistic worship of the sun god Aten, and had the city of Akhetaten built as the state's new capital. These extreme changes did not outlast his death, and Akhetaten—now a reminder of a strange, heretical aberration in Egypt's history—was abandoned quickly. In the Yucatan peninsula, where the complex city-polities that we call "the Maya" once ruled, there's a complex archaeological record of cities rising or falling in prominence due to wars and political struggles, but also perhaps to religious shifts and one pilgrimage site becoming more important than an earlier one (not that such changes are totally distinct from politics and war themselves).

Finally, I'd say that some places are "lost" in different ways than others. Early European archaeologists in the 19th century had a habit of crediting themselves with earth-shattering discoveries, but that doesn't mean they were amazing scholars who pieced together a puzzle of clues like Indiana Jones. A given abandoned temple may well have been a familiar local landmark to the people living near it, even if its cultural significance may have been lost, and the wealthy European may have done no more than ask where the cool old buildings were and announce their discovery back in their home country. To be fair, they may have done some actual work *analyzing* or *interpreting* what they saw, some more cleverly than others, but if you're wondering how something that large could be truly "lost"—sometimes, the answer is that it wasn't.