I know JTHipster was kidding in his comment, but he mentioned collateral damage and it was the first thing I was thinking of.

In WW2, the bombings of Dresden, Hamburg, Tokyo, London, and Hiroshima/Nagasaki were operations-- at that time--in the era's megacities relative to New York and Sao Paolo today. In fact some of those cities still are megacities today, and I think it's worth taking a serious consideration of why we wouldn't just firebomb or MOAB a city we're at war with, as we so proudly did then.

Wait. I know it sounds ridiculous, it probably is. But look, at present, we're either fighting guerilla-style enemies in the Middle East or tangoing with individual wildcards like DPRK and Iran. I think this article, and apparently that Strategic Studies Group, is considering military operations in megacities as a combination or similar style as today's aforementioned operations, and that's a fatal fantasy to be dreaming.

Now, unless we're hunting another Escobar, or fighting those ad-hoc militias that run the streets of corrupted cities like Sao Paolo, a war in a megacity would be a war, it would mean those cities of tens of millions have stumbled into something nasty and we're trying to neutralize something a LOT bigger than a cartel. In which case, I'd like to see if we really wouldn't be pulling another "it's for the greater good!" as we burn that megacity to the ground. Otherwise, we wouldn't be doubting the capabilities of the U.S. military. We wouldn't have to question if we can handle deploying a force "large enough" for an operation in a megacity to depose insurgents or cartel, cause we already know we damn well have it.