Sitting sixth, the Rebels face the third-placed Brumbies on Friday night in Canberra with flanker Brad Wilkin saying they wanted a maiden play-off berth locked away before a tricky assignment against the Drua in Fiji in the final round.
"Definitely, we want to control our own destiny here," Wilkin said.
"We don't want to have to get to the last round in Fiji and be relying on anything else.
"We're focused on getting down to Canberra and getting the win and then moving on to Fiji after that.
"We have a game that challenges the Brumbies and if we execute we have a game that we can take to them and internally we believe we can go well against them."
Among the changes, Melbourne welcome back Wallabies prop Taniela Tupou, via the bench, and Test fullback Andrew Kellaway, who both missed last round through concussion.
The Brumbies are bolstered by the returns of hooker Billy Pollard (knee) and winger Corey Toole (ankle) from injury, while lock Tom Hooper has been promoted to the starting 15.
A win over the Rebels would keep the ACT outfit's hopes of a top-two finish alive.
Meanwhile, the Queensland Reds have made a whopping eight changes to the starting line-up for Saturday night's clash with the Western Force at Suncorp Stadium.
Josh Flook returns at outside centre for his 50th Reds cap and Tom Lynagh is back at five-eighth.
Former All Blacks prop Alex Hodgman has been thrust into the starting XV after an 80-minute hitout for his club Sunnybank last weekend.
Wallabies hooker Matt Faessler is also back in the starting line-up after being among the players rested in last week's 28-19 loss to Fijian Drua.
The other inclusions to the XV are former All Blacks prop Jeffery Toomaga-Allen, lock Seru Uru, and wingers Mac Grealy and Tim Ryan.
The Force, fresh from their 27-7 demolition of the NSW Waratahs, have made just one change to their starting line-up with 20-year-old debutant winger Ronan Leahy replacing Chase Tiatia.
It could be another long afternoon for the Waratahs against the powerful Moana Pasifika scrum after NSW coach Darren Coleman was forced to blood two more rookie props.
After only playing his first match on loan from the Glasgow Warriors last week, former Argentine international Enrique Pieretto will miss Saturday's game in Auckland with a neck injury.
Already without every contracted front rower on his books, Coleman - told on Monday he wouldn't be offered a contract for 2025 - has had to call on Harry Lloyd from Brisbane Brothers and Michael Scott from Sydney's Shute Shield to make their debuts for the last-placed Waratahs.
