Well, sometimes that cannot be avoided. Everyone is liable to die, and while it's more likely that parents will die before their children, sometimes the opposite happens: a father, a mother, a Parental Substitute, etc. will be unable to stop the death of their son, daughter, ward, etc. and then will have to deal with the consequences.
The reasons, logically, can vary. At times, the "child" figure can succumb to illness. At others, they're done in by other living beings (humans, animals, aliens, etc.) in different circumstances. At others, they do themselves in. The key here is that this does NOT happen thanks to the parents' actions: either someone/something else does the younger person in. And the parents' reactions can vary as well, from depression to Despair Event Horizon crossing, to seeking Revenge against anyone who took the child away forever, etc.
Anime and Manga
- Astro Boy's whole plot is kicked off when Dr. Tenma's son Tobio dies in an accident and he creates Astro as a Replacement Goldfish.
- In the Cutey Honey first anime, Dr. Kisaragi used his dead daughter's image as a basis for Honey herself. Unlike Dr. Tenma, he loved Honey all the same and tells her so before dying.
- In the Nanoha franchise, Precia Testarossa completely lost it when her daughter Alicia died of illness. She first created Fate as a clone of her (and ended up abusing her for not being a copy of her "sister"), then centered her Mad Scientist plans on finding a way to actually revive her.
- Private Actress:
- The first chapter has Shiho being hired by a rich man's secretary to impersonate a girl named Miyuu who's supposed to have died with her mother in terrible and weird circumstances, and whose body was never found. The girl's father, Sendou, is about to die of illness and his biggest wish is to see Miyuu one last time... so the secretary asks Shiho to pretend to be a living Miyuu so he'll die happy. The man does realize that Shiho isn't Miyuu, but doesn't tell her to her face; after his death, aside of her pay she's is given a poetry book and a letter where he explains this and thanks Shiho for being by his side in his last days.
- Another case plays with it and Reincarnation: an artisan's eldest daughter was the victim of a Serial Killer 16 years ago and he pretty much went mad as a result (plus he's implied to suffer memory gaps due to brain damage after an accident), so the man's now-adult youngest daughter hires Shiho to pretend that she is the reincarnation of her late sister and help the emotionally-shattered father to deal with the cruel loss. Not only it works, but they find the killer and capture him.
- The Boarding School case involves the mysterious death of a junior high-aged Cute Bookworm, Fuyuka Sakuragi, whose parents suspect that she was literally bullied to death. So they hire Shiho to infiltrate the school and see if they're right. They are. And the culprit is the local Alpha Bitch, Kana Juumonji.
- Later in GoLion / Lion Voltron, two episodes involve dealing with the Team Dad Raible/Coran's biggest regret: the deaths/disappearances of both his wife and his infant son during the fall of Altea/Arus. Especially when a boy named Saint shows up and many leads point at him being said son, giving the team hope that the trope was averted... It wasn't: the guy's son had truly died, and the boy was either a Galra spy (GL) or an android (Voltron)
- At the very end, it turns out that Witch Honerva was the mother of Emperor Daibazaal. One finds out after Daibazaal's son Sincline has killed him (or better said, succeeded on getting him killed by the good guys), which gets her mad enough to betray her grandson. Logically, this is censored in Voltron.
- Halfway through the series, one of the Beastman was created from a woman from the Gorgon race, who had just lost her child and her people due to The Plague. Her maternal instincts were still intact, however, and she ends up bonding with Hiroshi.
- Digimon franchise:
- In the original, Koushiro Izumi was adopted by his uncle and aunt not only because of his parents' deaths, but because right around the same time said aunt and uncle lost their own baby son. They kept it a secret to not needlessly hurt him, but Koushirou found out anyway; later, they explain everything and say that they love him for their own person, not as a Replacement Goldfish.
- In 02, Ken Ichijouji's older brother Osamu was fatally hit by a car. Not only this doesn't "fix" Ken's The Unfavorite deal, but it saddles him with guilt since they had a huge fight few before his death.
- It regularly happens in the Gundam metaseries, of course:
- In the original one, Sovereign Degwin Zabi lost his third son Saslo in an assassination attempt (the same one that heavily scarred his second son Dozle) years before the series took place, and the death of his youngest son Garma in the war is what makes him fall in despair.
- In Mobile Suit Gundam SEED, Nicol Amalfi's parents Yuri and Romina are seen mourning for him after he dies in battle.
- MANY Sympathetic Murderers from Detective Conan fit here, killing their Asshole Victims for having caused the deaths of their children.
- Fullmetal Alchemist deals with this in all its incarnations:
- Pinako Rockbell's son and daughter-in-law, Winry's parents Yuriy and Sarah, were doctors who died in the Ishbalan War. The exact circumstances differ depending on the version: in the 2003 anime Roy was forced to execute them and ended up heavily traumatized over it; whereas in both the manga and the Brotherhood anime they were accidentally killed by a Scar who couldn't control his newfound alchemy powers (and had Scar not done it, Kimblee would've executed them anyway under orders of the higher-ups).
- Izumi and Sieg's son was a stillborn, and Izumi's reason to be an Ill Girl is that she lost her reproductory organs when she tried an Equivalent Exchange to revive him. She also tells the Elrics that she empathizes with their desire to bring back their Missing Mom due to this.
- In the 2003 anime, Envy is the Homunculus "born" from Dante and Hohenheim's attempt to recover their lost son, whereas Wrath is the "product" of Izumi's own try to do the same.
- The mangas by Mitsuru Adachi use this trope at least twice as Wham! Episodes:
- In Touch, the youngest Uesugi twin, Kazuya, gets fatally hit by a car 1/3 into the story. This means Shingo and Haruko outlive their kid, and his older brother Tatsuya becomes an Angsty Surviving Twin.
- Everything in Cross Game changes when Wakaba, the Tsukishima family's second daughter and Kou's girlfriend, dies in a summer camp accident at the end of the first part.
- The plot of Ano Hana begins years after the death of Meiko/Menma. Her parents Manabu and Irene have quite the difficulties handling their grief over her. Especially the latter
- In Ooku, several of Ienari's kids die. His wife Shige totally loses it when not only her son perishes, but she's accused of having killed him to frame her husband's mistress O-Shiga. The real killer is Ienari's mother Harusada. And it turns out Shige is not as crazy as she pretends to be, and in fact both she AND O-Shiga are planning their Revenge...
- Pictured above: the Pietá by Michelangelo, representing Mary holding on her son Jesus' corpse after he's laid down from his Cross.
- In Avengers: Infinity War, Thanos, with the exception of Nebula, outlives the entirety of the Black Order.
- Repeated in Avengers: Endgame, just, when Past!Thanos is the last of the time travellers to disintegrate.
- Though she's not his biological mother, Aunt Cass outlives Tadashi in Big Hero 6.
- The Bible, logically, has multiple examples. The most famous ones include: the deaths of all the Egyptian firstborns as a part of the Ten Plagues, Naomi losing her two sons (one of them being Ruth's first husband), the resurrection of a boy whose widow mom is friends with the prophet Elisha, the deaths of at least three of David's sons (Amnon, Absalom, his unnamed first kid with Bathsheba), the ten brothers tortured to death by the Persian King Antioch's guards in front of their mother before she's killed as well, the Massacre of the Innocents where all the boys under two years old around Bethlehem were executed under Herod's orders, the death and raising of Jairus's Ill Girl daughter, Jesus' own death in the Cross in front of his mother Mary, etc.
- In Doctor Who, it's mentioned that the entirety of the Doctor's biological family is dead, presumably including his children. Gallifrey later shows up safe and sound but there's no mention of his family.
- In Game of Thrones, all three of Cersei and Jamie's children die.
- Clifford and Penelope Blossom outlive poor Jason in Riverdale. Because Clifford killed him.
- Grand Pear (Applejack's maternal grandfather) in My Little Pony: Friendship Is Magic. To be fair, Applejack's parents are never outright said to have passed, but it's pretty heavily implied.
- In The Simpsons, both Homer and Abe express the hope that they'll outlive their children.
- Much to White Diamond's horror in Steven Universe, Pink Diamond is gone, fulfilling this trope.
- In Trollhunters, Gunmar is enraged to learn that Bular died before him.
- Queen Honerva aka Haggar in Voltron: Legendary Defender suffered from The Dark Side Will Make You Forget for most of the series. When she gets her memories back, and pulls Sincline out of the Quintessence Field, she's heartbroken to find that her son Lotor is dead.
- Enzo Ferrari famously outlived his son Alfredo "Dino" Ferrari who passed at 24. In his honour, Ferrari named an engine he'd worked on, the Dino.