Learn Russian: Обычно мы работаем с пятьюдесятью клиентами и двадцатью партнёрами. - We usually work with fifty clients and twenty partners.

Пятьдесят (fifty) is a compound number made of two parts. When declining numbers from 50 to 80 in oblique cases like the instrumental, you must decline both halves of the word! So the first half пять becomes пятью, and the second half declines like the number ten (десятью), combining into пятьюдесятью.

Why does двадцать only change at the very end to become двадцатью?

Unlike the numbers 50-80, the numbers 11-30 are not treated as having two declinable halves. They decline exactly like regular feminine nouns ending in a soft sign (like вещь or тетрадь). To form the instrumental case of двадцать, you simply keep the soft sign and add -ю at the end.

Why are the nouns клиентами and партнёрами in the instrumental case? Shouldn't numbers like 50 and 20 take the genitive plural?

Numbers only force the following noun into the genitive case when the number itself is in the nominative or inanimate accusative. In all other cases (the oblique cases), the number and the noun must agree! Since the preposition с (with) requires the instrumental case, both the numbers (пятьюдесятью, двадцатью) and their nouns (клиентами, партнёрами) take the instrumental case.

Why do we need the preposition с here? Doesn't the instrumental case already mean 'with'?