Sam Fisher's appearance in Ghost Recon Wildlands caused quite a stir but no one really expect Sam to break the fourth wall and start the feel train's engines when he figures out he is the only stealth action hero after Snake's retirement.
Video above shows Karen Bowman debriefing Sam Fisher and one of the Ghosts after the Splinter Cell crossover mission. At one point we see Sam saying "They don't make them like me anymore" after which he continues vaguely describing Solid Snake by saying "There was this other guy though - Army infiltration, he wore a bandana or something".
At this point Bowman tells him that the guy retired, leading Sam to a scary realisation - there is only him left. Ubisoft definitely put some work there to make the scene sad, as you can see on the screenshot below, but the full sensation comes only coupled with Sam's sad voice in the video.
This is a reference to Hideo Kojima's statement that the Metal Gear saga, and with it Snake's story, is over after he parted ways with Konami. This fact was further cemented by Metal Gear Survive's abysmal reception and sales that pretty much put the final nail in the franchise's coffin.
Metal Gear and Splinter Cell were the last and also the most popular stealth action hero sagas in modern gaming and maybe in gaming altogether. Since Big Boss essentially retired from field work long time ago and Venom Snake was killed by Solid Snake in 1995, Sam Fisher and Solid Snake remained the only stealth action heroes for a long time, with Gabriel Logan briefly jumping into the fold.
With no new Syphon Filter games for over ten years and the Metal Gear franchise now in the dust, Sam Fisher is effectively the only active spook left, which lead to his startling realisation in the cutscene.